@article {709656,
	title = {Automated neuron tracking inside moving and deforming animals using deep learning and targeted augmentation},
	journal = {Nature Methods},
	year = {In Press},
	abstract = {Advances in functional brain imaging now allow sustained rapid 3D visualization of large numbers of neurons inside behaving animals. To decode circuit activity, imaged neurons must be individually segmented and tracked. This is particularly challenging when the brain itself moves and deforms inside a flexible body. The field has lacked general methods for solving this problem effectively. To address this need, we developed a method based on a convolutional neural network (CNN) Awith specific enhancements which we apply to freely moving\&nbsp;Caenorhabditis elegans. For a traditional CNN to track neurons across images of a brain with different postures, the CNN must be trained with ground truth (GT) annotations of similar postures. When these postures are diverse, an adequate number of GT annotations can be prohibitively large to generate manually. We introduce {\textquoteleft}targeted augmentation{\textquoteright}, a method to automatically synthesize reliable annotations from a few manual annotations. Our method effectively learns the internal deformations of the brain. The learned deformations are used to synthesize annotations for new postures by deforming the manual annotations of similar postures in GT images. The technique is germane to 3D images, which are generally more difficult to analyze than 2D images. The synthetic annotations, which are added to diversify training datasets, drastically reduce manual annotation and proofreading. Our method is effective both when neurons are represented as individual points or as 3D volumes. We provide a GUI that incorporates targeted augmentation in an end-to-end pipeline, from manual GT annotation of a few images to final proofreading of all images. We apply the method to simultaneously measure activity in the second-layer interneurons in\&nbsp;C. elegans: RIA, RIB, and RIM, including the RIA neurite. We find that these neurons show rich behaviors, including switching entrainment on and off dynamically when the animal is exposed to periodic odor pulses.},
	author = {C. F. Park and M. B. Keshteli and K. Korchagina and A. Delrocq and V. Susoy and C. L. Jones and Samuel, A.D.T. and S. J. Rahi}
}
@article {663460,
	title = {Extracting neural signals from semi-immobilized animals with deformable non-negative matrix factorization},
	journal = {bioRxiv},
	year = {Submitted},
	month = {08 July 2020},
	abstract = {Extracting calcium traces from populations of neurons is a critical step in the study of the large-scale neural dynamics that govern behavior. Accurate activity extraction requires the correction of motion and movement-induced deformations as well as demixing of signals that may overlap spatially due to limitations in optical resolution. Traditionally, non-negative matrix factorization (NMF) methods have been successful in demixing and denoising cellular calcium activity in relatively motionless or pre-registered videos. However, standard NMF methods fail in animals undergoing significant non-rigid motion; similarly, standard image registration methods based on template matching can fail when large changes in activity lead to mismatches with the image template. To address these issues simultaneously, we introduce a deformable non-negative matrix factorization (dNMF) framework that jointly optimizes registration with signal demixing. On simulated data and real semi-immobilized\&nbsp;C. elegans\&nbsp;microscopy videos, dNMF outperforms traditional demixing methods that account for motion and demixing separately. Finally, following the extraction of neural traces from multiple imaging experiments, we develop a quantile regression time-series normalization technique to account for varying neural signal intensity baselines across different animals or different imaging setups. Open source code implementing this pipeline is available at\&nbsp;https://github.com/amin-nejat/dNMF.},
	author = {Amin Nejatbakhsh and Erdem Varol and Eviatar Yemini and Vivek Venkatachalam and Lin, Albert and Aravinthan D. T. Samuel and Liam Paninski}
}
@article {709716,
	title = {Synchronized strobed phase contrast and fluorescence microscopy: The interlaced standard reimagined},
	journal = {Optics Express},
	volume = {31},
	number = {4},
	year = {2023},
	pages = {5167-5180},
	abstract = {We propose a simple, cost-effective method for synchronized phase contrast and fluorescence video acquisition in live samples. Counter-phased pulses of phase contrast illumination and fluorescence excitation light are synchronized with the exposure of the two fields of an interlaced camera sensor. This results in a video sequence in which each frame contains both exposure modes, each in half of its pixels. The method allows real-time acquisition and display of synchronized and spatially aligned phase contrast and fluorescence image sequences that can be separated by de-interlacing in two independent videos. The method can be implemented on any fluorescence microscope with a camera port without needing to modify the optical path.},
	url = {https://doi.org/10.1364/OE.474045},
	author = {Hosu, B.G. and W. Hill and Samuel, A. D. and Berg, H.C.}
}
@article {709661,
	title = {Functional imaging and quantification of multineuronal olfactory responses in C. elegans},
	journal = {Science Advances},
	volume = {9},
	number = {9},
	year = {2023},
	pages = {eade1249},
	abstract = {Many animals perceive odorant molecules by collecting information from ensembles of olfactory neurons, where each neuron uses receptors that are tuned to recognize certain odorant molecules with different binding affinity. Olfactory systems are able, in principle, to detect and discriminate diverse odorants using combinatorial coding strategies. We have combined microfluidics and multineuronal imaging to study the ensemble-level olfactory representations at the sensory periphery of the nematode\&nbsp;Caenorhabditis elegans. The collective activity of\&nbsp;C. elegans\&nbsp;chemosensory neurons reveals high-dimensional representations of olfactory information across a broad space of odorant molecules. We reveal diverse tuning properties and dose-response curves across chemosensory neurons and across odorants. We describe the unique contribution of each sensory neuron to an ensemble-level code for volatile odorants. We show that a natural stimuli, a set of nematode pheromones, are also encoded by the sensory ensemble. The integrated activity of the\&nbsp;C. elegans\&nbsp;chemosensory neurons contains sufficient information to robustly encode the intensity and identity of diverse chemical stimuli.},
	url = {https://doi.org/10.1126/sciadv.ade1249},
	author = {Lin, A. and S. Qin and H. Casademunt and Wu, M. and W. Hung and G. Cain and N. Z. Tan and R. Valenzuela and L. Lesan- pezeshki and V. Venkatachalam and C. Pehlevan and M. Zhen and Samuel, A. D.}
}
@article {709651,
	title = {Membrain: An interactive deep learning matlab tool for connectomic segmentation on commodity desktops},
	journal = {Frontiers in Neural Circuits},
	volume = {17},
	year = {2023},
	abstract = {Connectomics is fundamental in propelling our understanding of the nervous system{\textquoteright}s organization, unearthing cells and wiring diagrams reconstructed from volume electron microscopy (EM) datasets. Such reconstructions, on the one hand, have benefited from ever more precise automatic segmentation methods, which leverage sophisticated deep learning architectures and advanced machine learning algorithms. On the other hand, the field of neuroscience at large, and of image processing in particular, has manifested a need for user-friendly and open source tools which enable the community to carry out advanced analyses. In line with this second vein, here we propose mEMbrain, an interactive MATLAB-based software which wraps algorithms and functions that enable labeling and segmentation of electron microscopy datasets in a user-friendly user interface compatible with Linux and Windows. Through its integration as an API to the volume annotation and segmentation tool VAST, mEMbrain encompasses functions for ground truth generation, image preprocessing, training of deep neural networks, and on-the-fly predictions for proofreading and evaluation. The final goals of our tool are to expedite manual labeling efforts and to harness MATLAB users with an array of semi-automatic approaches for instance segmentation. We tested our tool on a variety of datasets that span different species at various scales, regions of the nervous system and developmental stages. To further expedite research in connectomics, we provide an EM resource of ground truth annotation from four different animals and five datasets, amounting to around 180 h of expert annotations, yielding more than 1.2 GB of annotated EM images. In addition, we provide a set of four pre-trained networks for said datasets. All tools are available from\&nbsp;https://lichtman.rc.fas.harvard.edu/mEMbrain/. With our software, our hope is to provide a solution for lab-based neural reconstructions which does not require coding by the user, thus paving the way to affordable connectomics.},
	url = {https://doi.org/10.3389/fncir.2023.952921},
	author = {E. C. Pavarino and Yang, E. and N. Dhanyasi and M. D. Wang and F. Bidel and Lu, X. and F. Yang and C. Francisco Park and M. Bangalore Renuka and B. Drescher and Samuel, A.D.T. and B. Hochner and P. S. Katz and M. Zhen and J. W. Lichtman and Y. Meirovitch}
}
@article {709646,
	title = {Evolutionarily conserved behavioral plasticity enables context- dependent mating in C. elegans},
	journal = {Current Biology},
	volume = {33},
	number = {20},
	year = {2023},
	pages = {4532-4537.E3},
	abstract = {Behavioral plasticity helps humans and animals to achieve their goals by adapting their behaviors to different environments. Although behavioral plasticity is ubiquitous, many innate species-specific behaviors, such as mating, are often assumed to be stereotyped and unaffected by plasticity or learning, especially in invertebrates. Here, we describe a novel case of behavioral plasticity in the nematode\&nbsp;C. elegans\&nbsp;{\textendash} under a different set of naturalistic conditions the male uses a unique, previously undescribed set of behavioral steps for mating. Under standard lab conditions (agar plates with bacterial food), the male performs parallel mating, a largely two-dimensional behavioral strategy where his body and tail remain flat on the surface and slide alongside the partner {\textquoteleft}s body from initial contact to copulation. But when placed in liquid medium, the male performs spiral mating, a distinctly three-dimensional behavioral strategy where he winds around the partner {\textquoteright}s body in a helical embrace. The performance of spiral mating does not require a long-term change in growing conditions but it does improve with experience. This experience-dependent improvement involves a critical period {\textendash} a time window around the L4 to early adult stage, which coincides with the development of most male-specific neurons. We tested several wild isolates of\&nbsp;C. elegans\&nbsp;and other\&nbsp;Caenorhabditis\&nbsp;species and found that most were capable of parallel mating on surfaces and spiral mating in liquids. We suggest that two- and three-dimensional mating strategies in\&nbsp;Caenorhabditis\&nbsp;are plastic, conditionally expressed phenotypes conserved across the genus, and which can be genetically {\textquotedblleft}fixed {\textquotedblright} in some species.},
	url = {https://www.cell.com/current-biology/fulltext/S0960-9822(23)01216-2},
	author = {V. Susoy and Samuel, A. D.}
}
@article {709641,
	title = {Pezo-1 and trp-4 mechanosensors are involved in mating behavior in C. elegans},
	journal = {PNAS Nexus},
	volume = {1},
	number = {5},
	year = {2022},
	abstract = {Male mating in\&nbsp;Caenorhabditis elegans\&nbsp;is a complex behavior with a strong mechanosensory component.\&nbsp;C. elegans\&nbsp;has several characterized mechanotransducer proteins, but few have been shown to contribute to mating. Here, we investigated the roles of\&nbsp;PEZO-1, a piezo channel, and\&nbsp;TRP-4, a mechanotransducing TRPN channel, in male mating behavior. We show that\&nbsp;pezo-1\&nbsp;is expressed in several male-specific neurons with known roles in mating. We show that, among other neurons,\&nbsp;trp-4\&nbsp;is expressed in the Post-Cloacal sensilla neuron type A (PCA) sensory neuron, which monitors relative sliding between the male and the hermaphrodite and inhibits neurons involved in vulva detection. Mutations in both genes compromise many steps of mating, including initial response to the hermaphrodite, scanning, turning, and vulva detection. We performed pan-neuronal imaging during mating between freely moving mutant males and hermaphrodites. Both\&nbsp;pezo-1\&nbsp;and\&nbsp;trp-4\&nbsp;mutants showed spurious activation of the sensory neurons involved in vulva detection. In\&nbsp;trp-4\&nbsp;mutants, this spurious activation might be caused by PCA failure to inhibit vulva-detecting neurons during scanning. Indeed, we show that without functional\&nbsp;TRP-4, PCA fails to detect the relative sliding between the male and hermaphrodite. Cell-specific\&nbsp;TRP-4\&nbsp;expression restores PCA{\textquoteright}s mechanosensory function. Our results demonstrate new roles for both\&nbsp;PEZO-1\&nbsp;and\&nbsp;TRP-4\&nbsp;mechanotransducers in\&nbsp;C. elegans\&nbsp;mating behavior.},
	url = {https://doi.org/10.1093/pnasnexus/pgac213},
	author = {K. I. Brugman and V. Susoy and A. J. Whittaker and W. Palma and S. Nava and Samuel, A.D.T. and P. W. Sternberg}
}
@article {709601,
	title = {Extrasynaptic signaling enables an asymmetric juvenile motor circuit to produce symmetric undulation},
	journal = {Current Biology},
	volume = {31},
	number = {21},
	year = {2022},
	pages = {4631-4644.E5},
	abstract = {In many animals, there is a direct correspondence between the motor patterns that drive locomotion and the motor neuron innervation. For example, the adult C. elegans moves with symmetric and alternating dorsal-ventral bending waves arising from symmetric motor neuron input onto the dorsal and ventral muscles. In contrast to the adult, the C. elegans motor circuit at the juvenile larval stage has asymmetric wiring between motor neurons and muscles but still generates adult-like bending waves with dorsal-ventral symmetry. We show that in the juvenile circuit, wiring between excitatory and inhibitory motor neurons coordinates the contraction of dorsal muscles with relaxation of ventral muscles, producing dorsal bends. However, ventral bending is not driven by analogous wiring. Instead, ventral muscles are excited uniformly by premotor interneurons through extrasynaptic signaling. Ventral bends occur in anti-phasic entrainment to activity of the same motor neurons that drive dorsal bends. During maturation, the juvenile motor circuit is replaced by two motor subcircuits that separately drive dorsal and ventral bending. Modeling reveals that the juvenile{\textquoteright}s immature motor circuit is an adequate solution to generate adult-like dorsal-ventral bending before the animal matures. Developmental rewiring between functionally degenerate circuit solutions, which both generate symmetric bending patterns, minimizes behavioral disruption across maturation.},
	url = {https://doi.org/10.1016/j.cub.2022.09.002},
	author = {Y. Lu and T. Ahamed and B. Mulcahy and Meng, J. and D. Witvliet and S. A. Guan and D. Holmyard and W. Hung and Q. Wen and A. D. Chisholm and Samuel, A.D.T. and M. Zhen}
}
@article {709591,
	title = {Post-embryonic remodeling of the c. elegans motor circuit},
	journal = {Current biology},
	volume = {32},
	number = {21},
	year = {2022},
	pages = {4645{\textendash}4659.e3},
	abstract = {During development, animals can maintain behavioral output even as underlying circuitry structurally remodels. After hatching, C. elegans undergoes substantial motor neuron expansion and synapse rewiring while the animal continuously moves with an undulatory pattern. To understand how the circuit transitions from its juvenile to mature configuration without interrupting functional output, we reconstructed the C. elegans motor circuit by electron microscopy across larval development. We observed the following: First, embryonic motor neurons transiently interact with the developing post-embryonic motor neurons prior to remodeling of their juvenile wiring. Second, post-embryonic neurons initiate synapse development with their future partners as their neurites navigate through the juvenile nerve cords. Third, embryonic and post-embryonic neurons sequentially build structural machinery needed for the adult circuit before the embryonic neurons relinquish their roles to post-embryonic neurons. Fourth, this transition is repeated region by region along the body in an anterior-to-posterior sequence, following the birth order of neurons. Through this orchestrated and programmed rewiring, the motor circuit gradually transforms from asymmetric to symmetric wiring. These maturation strategies support the continuous maintenance of motor patterns as the juvenile circuit develops into the adult configuration.},
	url = {https://doi.org/10.1016/j.cub.2023.09.003},
	author = {B. Mulcahy and D. K. Witvliet and Mitchell, J. and R. Schalek and D. R. Berger and Wu, Y. and D. Holmyard and Y. Lu and T. Ahamed and Samuel, A. D. and A. D. Chisholm and J. W. Lichtman and M. Zhen}
}
@article {Lin2022,
	title = {Imaging whole-brain activity to understand behaviour},
	journal = {Nature Reviews Physics},
	volume = {4},
	year = {2022},
	pages = {292{\textendash}305},
	abstract = {Until now, most brain studies have focused on small numbers of neurons that interact in limited circuits, allowing analysis of individual computations or steps of neural processing. During behaviour, however, brain activity must integrate multiple circuits in different brain regions. Whole-brain recording with cellular resolution provides a new opportunity to dissect the neural basis of behaviour, but whole-brain activity is mutually contingent on behaviour itself, especially for natural behaviours such as navigation, mating or hunting, which require dynamic interaction between the animal, its environment and other animals. Many of the signalling and feedback pathways that animals use to guide behaviour only occur in freely moving animals. Recent technological advances have enabled whole-brain recording in small behaving animals including the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster and the larval zebrafish Danio rerio. These whole-brain experiments capture neural activity with cellular resolution spanning sensory, decision-making and motor circuits, and thereby demand new theoretical approaches that integrate brain dynamics with behavioural dynamics. We review the experimental and theoretical methods used to understand animal behaviour and whole-brain activity, and the opportunities for physics to contribute to this emerging field of systems neuroscience.},
	issn = {2522-5820},
	doi = {10.1038/s42254-022-00430-w},
	url = {https://doi.org/10.1038/s42254-022-00430-w},
	author = {Lin, Albert and Witvliet, Daniel and Hernandez-Nunez, Luis and Linderman, Scott W and Aravinthan D T Samuel and Vivek Venkatachalam}
}
@article {10.7554/eLife.62567,
	title = {Circuits for integrating learned and innate valences in the insect brain},
	journal = {eLife},
	volume = {10},
	year = {2021},
	month = {nov},
	pages = {e62567},
	publisher = {eLife Sciences Publications, Ltd},
	abstract = {Animal behavior is shaped both by evolution and by individual experience. Parallel brain pathways encode innate and learned valences of cues, but the way in which they are integrated during action-selection is not well understood. We used electron microscopy to comprehensively map with synaptic resolution all neurons downstream of all mushroom body (MB) output neurons (encoding learned valences) and characterized their patterns of interaction with lateral horn (LH) neurons (encoding innate valences) in \textitDrosophila larva. The connectome revealed multiple \textitconvergence neuron types that receive convergent MB and LH inputs. A subset of these receives excitatory input from positive-valence MB and LH pathways and inhibitory input from negative-valence MB pathways. We confirmed functional connectivity from LH and MB pathways and behavioral roles of two of these neurons. These neurons encode integrated odor value and bidirectionally regulate turning. Based on this, we speculate that learning could potentially skew the balance of excitation and inhibition onto these neurons and thereby modulate turning. Together, our study provides insights into the circuits that integrate learned and innate valences to modify behavior.},
	keywords = {action selection, Connectome, learnt behavior, valence},
	issn = {2050-084X},
	doi = {10.7554/eLife.62567},
	url = {https://doi.org/10.7554/eLife.62567},
	author = {Eschbach, Claire and Fushiki, Akira and Winding, Michael and Bruno Afonso and Andrade, Ingrid V and Cocanougher, Benjamin T and Eichler, Katharina and Gepner, Ruben and Si, Guangwei and Valdes-Aleman, Javier and Fetter, Richard D and Marc Gershow and Jefferis, Gregory SXE and Aravinthan D T Samuel and James W Truman and Cardona, Albert and Zlatic, Marta},
	editor = {VijayRaghavan, K}
}
@article {Witvliet2020.04.30.066209,
	title = {Connectomes across development reveal principles of brain maturation},
	journal = {Nature},
	volume = {596},
	year = {2021},
	pages = {257{\textendash}261},
	publisher = {Cold Spring Harbor Laboratory},
	abstract = {From birth to adulthood, an animal{\textquoteright}s nervous system changes as its body grows and its behaviours mature. The form and extent of circuit remodelling across the connectome is unknown. We used serial-section electron microscopy to reconstruct the full brain of eight isogenic C. elegans individuals across postnatal stages to learn how it changes with age. The overall geometry of the brain is preserved from birth to adulthood. Upon this constant scaffold, substantial changes in chemical synaptic connectivity emerge. Comparing connectomes among individuals reveals substantial connectivity differences that make each brain partly unique. Comparing connectomes across maturation reveals consistent wiring changes between different neurons. These changes alter the strength of existing connections and create new connections. Collective changes in the network alter information processing. Over development, the central decision-making circuitry is maintained whereas sensory and motor pathways substantially remodel. With age, the brain progressively becomes more feedforward and discernibly modular. Developmental connectomics reveals principles that underlie brain maturation.Competing Interest StatementThe authors have declared no competing interest.},
	doi = {10.1101/2020.04.30.066209},
	url = {https://www.nature.com/articles/s41586-021-03778-8},
	author = {Witvliet, Daniel and Ben Mulcahy and Mitchell, James K. and Meirovitch, Yaron and Berger, Daniel R. and Wu, Yuelong and Liu, Yufang and Koh, Wan Xian and Parvathala, Rajeev and Douglas Holmyard and Schalek, Richard L. and Shavit, Nir and Chisholm, Andrew D. and Lichtman, Jeff W. and Aravinthan D. T. Samuel and Mei Zhen}
}
@article {Vogteabd6900,
	title = {Internal state configures olfactory behavior and early sensory processing in Drosophila larvae},
	journal = {Science Advances},
	volume = {7},
	number = {1},
	year = {2021},
	publisher = {American Association for the Advancement of Science},
	abstract = {Animals exhibit different behavioral responses to the same sensory cue depending on their internal state at a given moment. How and where in the brain are sensory inputs combined with state information to select an appropriate behavior? Here, we investigate how food deprivation affects olfactory behavior in Drosophila larvae. We find that certain odors repel well-fed animals but attract food-deprived animals and that feeding state flexibly alters neural processing in the first olfactory center, the antennal lobe. Hunger differentially modulates two output pathways required for opposing behavioral responses. Upon food deprivation, attraction-mediating uniglomerular projection neurons show elevated odor-evoked activity, whereas an aversion-mediating multiglomerular projection neuron receives odor-evoked inhibition. The switch between these two pathways is regulated by the lone serotonergic neuron in the antennal lobe, CSD. Our findings demonstrate how flexible behaviors can arise from state-dependent circuit dynamics in an early sensory processing center.},
	doi = {10.1126/sciadv.abd6900},
	url = {https://advances.sciencemag.org/content/7/1/eabd6900},
	author = {Katrin Vogt and David M. Zimmerman and Matthias Schlichting and Hernandez-Nunez, Luis and Qin, Shanshan and Karen Malacon and Michael Rosbash and Cengiz Pehlevan and Cardona, Albert and Aravinthan D. T. Samuel}
}
@article {Susoy2020.09.09.289454,
	title = {Natural sensory context drives diverse brain-wide activity during C. elegans mating},
	journal = {Cell},
	volume = {184},
	number = {20},
	year = {2021},
	pages = {P5122-5137.E17},
	publisher = {Cold Spring Harbor Laboratory},
	abstract = {Natural goal-directed behaviors often involve complex sequences of many stimulus-triggered components. Understanding how brain circuits organize such behaviors requires mapping the interactions between an animal, its environment, and its nervous system. Here, we use continuous brain-wide neuronal imaging to study the full performance of mating by the C. elegans male. We show that as each mating unfolds in its own sequence of component behaviors, the brain operates similarly between instances of each component, but distinctly between different components. When the full sensory and behavioral context is taken into account, unique roles emerge for each neuron. Functional correlations between neurons are not fixed, but change with behavioral dynamics. From the contribution of individual neurons to circuits, our study shows how diverse brain-wide dynamics emerge from the integration of sensory perception and motor actions within their natural context.Competing Interest StatementThe authors have declared no competing interest.},
	doi = {10.1101/2020.09.09.289454},
	url = {https://doi.org/10.1016/j.cell.2021.08.024},
	author = {Susoy, Vladislav and Wesley Hung and Witvliet, Daniel and Whitener, Joshua E. and Wu, Min and Graham, Brett J. and Mei Zhen and Vivek Venkatachalam and Aravinthan D. T. Samuel}
}
@article {10.7554/eLife.68848,
	title = {Corollary discharge promotes a sustained motor state in a neural circuit for navigation},
	journal = {eLife},
	volume = {10},
	year = {2021},
	month = {apr},
	pages = {e68848},
	publisher = {eLife Sciences Publications, Ltd},
	abstract = {Animals exhibit behavioral and neural responses that persist on longer timescales than transient or fluctuating stimulus inputs. Here, we report that \textitCaenorhabditis elegans uses feedback from the motor circuit to a sensory processing interneuron to sustain its motor state during thermotactic navigation. By imaging circuit activity in behaving animals, we show that a principal postsynaptic partner of the AFD thermosensory neuron, the AIY interneuron, encodes both temperature and motor state information. By optogenetic and genetic manipulation of this circuit, we demonstrate that the motor state representation in AIY is a corollary discharge signal. RIM, an interneuron that is connected with premotor interneurons, is required for this corollary discharge. Ablation of RIM eliminates the motor representation in AIY, allows thermosensory representations to reach downstream premotor interneurons, and reduces the animal{\textquoteright}s ability to sustain forward movements during thermotaxis. We propose that feedback from the motor circuit to the sensory processing circuit underlies a positive feedback mechanism to generate persistent neural activity and sustained behavioral patterns in a sensorimotor transformation.},
	keywords = {corollary discharge, efferency copy, thermotaxis},
	issn = {2050-084X},
	doi = {10.7554/eLife.68848},
	url = {https://doi.org/10.7554/eLife.68848},
	author = {Ni Ji and Vivek Venkatachalam and Rodgers, Hillary Denise and Wesley Hung and Taizo Kawano and Clark, Christopher M and Lim, Maria and Mark J. Alkema and Mei Zhen and Aravinthan D T Samuel},
	editor = {Zimmer, Manuel and Calabrese, Ronald L}
}
@article {Hernandez-Nunez2020.07.09.196428,
	title = {Synchronous and opponent thermosensors use flexible cross-inhibition to orchestrate thermal homeostasis},
	journal = {Science Advances},
	volume = {7},
	number = {35},
	year = {2021},
	publisher = {Cold Spring Harbor Laboratory},
	abstract = {Body temperature homeostasis is an essential function that relies upon the integration of the outputs from multiple classes of cooling- and warming-responsive cells. The computations that integrate these diverse outputs to control body temperature are not understood. Here we discover a new set of Warming Cells (WCs), and show that the outputs of these WCs and previously described Cooling Cells (CCs1) are combined in a cross-inhibition computation to drive thermal homeostasis in larval Drosophila. We find that WCs and CCs are opponent sensors that operate in synchrony above, below, and near the homeostatic set-point, with WCs consistently activated by warming and inhibited by cooling, and CCs the converse. Molecularly, these opponent sensors rely on overlapping combinations of Ionotropic Receptors to detect temperature changes: Ir68a, Ir93a, and Ir25a for WCs; Ir21a, Ir93a, and Ir25a for CCs. Using a combination of optogenetics, sensory receptor mutants, and quantitative behavioral analysis, we find that the larva uses flexible cross-inhibition of WC and CC outputs to locate and stay near the homeostatic set-point. Balanced cross-inhibition near the set-point suppresses any directed movement along temperature gradients. Above the set-point, WCs mediate avoidance to warming while cross-inhibiting avoidance to cooling. Below the set-point, CCs mediate avoidance to cooling while cross-inhibiting avoidance to warming. Our results demonstrate how flexible cross-inhibition between warming and cooling pathways can orchestrate homeostatic thermoregulation.Competing Interest StatementThe authors have declared no competing interest.},
	doi = {10.1101/2020.07.09.196428},
	url = {https://www.science.org/doi/10.1126/sciadv.abg6707$\#$:~:text=DOI\%3A\%2010.1126/sciadv.abg6707},
	author = {Hernandez-Nunez, Luis and Chen, Alicia and Budelli, Gonzalo and Richter, Vincent and Rist, Anna and Thum, Andreas S. and Mason Klein and Garrity, Paul and Aravinthan D. T. Samuel}
}
@conference {10.1007/978-3-030-59722-1_2,
	title = {Demixing Calcium Imaging Data in C. elegans via Deformable Non-negative Matrix Factorization},
	booktitle = {Medical Image Computing and Computer Assisted Intervention {\textendash} MICCAI 2020},
	year = {2020},
	pages = {14{\textendash}24},
	publisher = {Springer International Publishing},
	organization = {Springer International Publishing},
	address = {Cham},
	abstract = {Extracting calcium traces from the neurons of C. elegans is an important problem, enabling the study of individual neuronal activity and the large-scale dynamics that govern behavior. Traditionally, non-negative matrix factorization (NMF) methods have been successful in demixing and denoising cellular calcium activity in relatively motionless or pre-registered videos. However, in the case of C. elegans or other animal models where motion compensation methods fail to stabilize the effect of even mild motion in the imaging data, standard NMF methods fail to capture cellular footprints since these footprints are variable in time. In this work, we introduce deformable non-negative matrix factorization (dNMF), which models the motion trajectory of the underlying image space using a polynomial basis function. Spatial footprints and neural activity are optimized jointly with motion trajectories in a matrix tri-factorization setting. On simulated data, dNMF is demonstrated to outperform currently available demixing methods as well as methods that account for motion and demixing separately. Furthermore, we display the practical utility of our approach in extracting calcium traces from C. elegans microscopy videos. The extracted traces elucidate spontaneous neural\&nbsp;activity as well as responses to stimuli. Open source code implementing this pipeline is available at https://github.com/amin-nejat/dNMF},
	isbn = {978-3-030-59722-1},
	url = {https://link.springer.com/chapter/10.1007\%2F978-3-030-59722-1_2},
	author = {Amin Nejatbakhsh and Erdem Varol and Eviatar Yemini and Vivek Venkatachalam and Lin, Albert and Aravinthan D. T. Samuel and Oliver Hobert and Liam Paninski},
	editor = {Anne L. Martel and Abolmaesumi, Purang and Stoyanov, Danail and Mateus, Diana and Zuluaga, Maria A. and Zhou, S. Kevin and Racoceanu, Daniel and Joskowicz, Leo}
}
@conference {10.1007/978-3-030-59722-1_8,
	title = {Learning Guided Electron Microscopy with Active Acquisition},
	booktitle = {Medical Image Computing and Computer Assisted Intervention {\textendash} MICCAI 2020},
	year = {2020},
	pages = {77{\textendash}87},
	publisher = {Springer International Publishing},
	organization = {Springer International Publishing},
	address = {Cham},
	abstract = {Single-beam scanning electron microscopes (SEM) are widely used to acquire massive datasets for biomedical study, material analysis, and fabrication inspection. Datasets are typically acquired with uniform acquisition: applying the electron beam with the same power and duration to all image pixels, even if there is great variety in the pixels{\textquoteright} importance for eventual use. Many SEMs are now able to move the beam to any pixel in the field of view without delay, enabling them, in principle, to invest their time budget more effectively with non-uniform imaging.},
	isbn = {978-3-030-59722-1},
	url = {https://link.springer.com/chapter/10.1007\%2F978-3-030-59722-1_8},
	author = {Mi, Lu and Wang, Hao and Meirovitch, Yaron and Richard Schalek and Turaga, Srinivas C. and Lichtman, Jeff W. and Aravinthan D. T. Samuel and Shavit, Nir},
	editor = {Anne L. Martel and Abolmaesumi, Purang and Stoyanov, Danail and Mateus, Diana and Zuluaga, Maria A. and Zhou, S. Kevin and Racoceanu, Daniel and Joskowicz, Leo}
}
@article {663458,
	title = {NeuroPAL: A Neuronal Polychromatic Atlas of Landmarks for Whole-Brain Imaging in C. elegans},
	journal = {Cell},
	volume = {184},
	number = {1},
	year = {2020},
	month = {07 January 2021},
	pages = {272-288},
	abstract = {Comprehensively resolving single neurons and their cellular identities from whole-brain fluorescent images is a major challenge. We achieve this in\&nbsp;C. elegans\&nbsp;through the engineering and use of a multicolor transgene called NeuroPAL (a\&nbsp;Neuronal\&nbsp;Polychromatic\&nbsp;Atlas of\&nbsp;Landmarks). NeuroPAL worms share a stereotypical multicolor fluorescence map for the entire hermaphrodite nervous system that allows comprehensive determination of neuronal identities. Neurons labeled with NeuroPAL do not exhibit fluorescence in the green, cyan, or yellow emission channels, allowing the transgene to be used with numerous reporters of gene expression or neuronal dynamics. Here we showcase three studies that leverage NeuroPAL for nervous-system-wide neuronal identification. First, we determine the brainwide expression patterns of all metabotropic receptors for acetylcholine, GABA, and glutamate, completing a map of this communication network. Second, we uncover novel changes in cell fate caused by transcription factor mutations. Third, we record brainwide activity in response to attractive and repulsive chemosensory cues, characterizing multimodal coding and novel neuronal asymmetries for these stimuli. We present a software package that enables semi-automated determination of all neuronal identities based on color and positional information. The NeuroPAL framework and software provide a means to design landmark atlases for other tissues and organisms. In conclusion, we expect NeuroPAL to serve as an invaluable tool for gene expression analysis, neuronal fate studies, and for mapping whole-brain activity patterns.},
	url = {https://doi.org/10.1016/j.cell.2020.12.012/10.1101/676312v2},
	author = {Eviatar Yemini and Lin, Albert and Amin Nejatbakhsh and Erdem Varol and Ruoxi Sun and Gonzalo E. Mena and Aravinthan D. T. Samuel and Liam Paninski and Vivek Venkatachalam and Oliver Hobert}
}
@article {Choi2020,
	title = {Probing and manipulating embryogenesis via nanoscale thermometry and temperature control},
	journal = {Proceedings of the National Academy of Sciences},
	volume = {117},
	number = {26},
	year = {2020},
	month = {jun},
	pages = {14636-14641},
	publisher = {National Academy of Sciences},
	abstract = {Temperature is a key control parameter of biological processes, but measuring and controlling temperatures on a cellular-length scale in living organisms remains an outstanding challenge. Applying nanoscale-thermometry techniques to early embryos, we study cell divisions in a highly controlled manner using local laser heating and real-time in vivo temperature readout. Nitrogen-vacancy centers in nanodiamonds, incorporated into the cells, allow us to map out the temperature distribution of a locally heated embryo with submicrometer spatial resolution and high sensitivity. The simultaneous cell-division imaging under controlled laser heating is used to achieve cell-cycle timing control and inversion, providing insights into timing-regulation mechanisms during early embryogenesis. Understanding the coordination of cell-division timing is one of the outstanding questions in the field of developmental biology. One active control parameter of the cell-cycle duration is temperature, as it can accelerate or decelerate the rate of biochemical reactions. However, controlled experiments at the cellular scale are challenging, due to the limited availability of biocompatible temperature sensors, as well as the lack of practical methods to systematically control local temperatures and cellular dynamics. Here, we demonstrate a method to probe and control the cell-division timing in Caenorhabditis elegans embryos using a combination of local laser heating and nanoscale thermometry. Local infrared laser illumination produces a temperature gradient across the embryo, which is precisely measured by in vivo nanoscale thermometry using quantum defects in nanodiamonds. These techniques enable selective, controlled acceleration of the cell divisions, even enabling an inversion of division order at the two-cell stage. Our data suggest that the cell-cycle timing asynchrony of the early embryonic development in C. elegans is determined independently by individual cells rather than via cell-to-cell communication. Our method can be used to control the development of multicellular organisms and to provide insights into the regulation of cell-division timings as a consequence of local perturbations.},
	issn = {0027-8424},
	doi = {10.1073/PNAS.1922730117},
	url = {https://www.pnas.org/content/early/2020/06/12/1922730117},
	author = {Joonhee Choi and Hengyun Zhou and Renate Landig and Wu, Hai-Yin and Xiaofei Yu and Stephen E. Von Stetina and Georg Kucsko and Susan E. Mango and Daniel J. Needleman and Aravinthan D. T. Samuel and Peter C. Maurer and Park, Hongkun and Mikhail D. Lukin}
}
@article {629144,
	title = {Imaging whole nervous systems: insights into behavior from brains inside bodies},
	journal = {Nature Methods},
	volume = {16},
	number = {1},
	year = {2019},
	pages = {14-15},
	abstract = {The development of systems combining rapid volumetric imaging with three-dimensional tracking has enabled the measurement of brain-wide dynamics in freely behaving animals such as worms, flies, and fish. These advances provide an exciting opportunity to understand the organization of neural circuits in the context of voluntary and natural behaviors. In this Comment, we highlight recent progress in this burgeoning area of research.},
	url = {https://www.nature.com/articles/s41592-018-0276-8?WT.feed_name=subjects_neuroscience},
	author = {John A. Calarco and Aravinthan D. T. Samuel}
}
@article {BUDELLI2019,
	title = {Ionotropic Receptors Specify the Morphogenesis of Phasic Sensors Controlling Rapid Thermal Preference in Drosophila},
	journal = {Neuron},
	volume = {101},
	number = {4},
	year = {2019},
	pages = {738-747},
	abstract = {Thermosensation is critical for avoiding thermal extremes and regulating body temperature. While thermosensors activated by noxious temperatures respond to hot or cold, many innocuous thermosensors exhibit robust baseline activity and lack discrete temperature thresholds, suggesting they are not simply warm and cool detectors. Here, we investigate how the aristal Cold Cells encode innocuous temperatures in Drosophila. We find they are not cold sensors but cooling-activated and warming-inhibited phasic thermosensors that operate similarly at warm and cool temperatures; we propose renaming them {\textquotedblleft}Cooling Cells.{\textquotedblright} Unexpectedly, Cooling Cell thermosensing does not require the previously reported Brivido Transient Receptor Potential (TRP) channels. Instead, three Ionotropic Receptors (IRs), IR21a, IR25a, and IR93a, specify both the unique structure of Cooling Cell cilia endings and their thermosensitivity. Behaviorally, Cooling Cells promote both warm and cool avoidance. These findings reveal a morphogenetic role for IRs and demonstrate the central role of phasic thermosensing in innocuous thermosensation.},
	keywords = {iGluR, ionotropic receptor, Ir21a, Ir25a, Ir93a, Morphogenesis, sensory neuron, Temperature, thermoreceptor, thermosensation},
	issn = {0896-6273},
	doi = {https://doi.org/10.1016/j.neuron.2018.12.022},
	url = {https://doi.org/10.1016/j.neuron.2018.12.022},
	author = {Budelli, Gonzalo and Ni, Lina and Cristina Berciu and Lena van Giesen and Zachary A. Knecht and Elaine C. Chang and Benjamin Kaminski and Ana F. Silbering and Aravi Samuel and Mason Klein and Richard Benton and Daniela Nicastro and Garrity, Paul A.}
}
@article {SI2019,
	title = {Structured Odorant Response Patterns across a Complete Olfactory Receptor Neuron Population},
	journal = {Neuron},
	volume = {101},
	number = {5},
	year = {2019},
	pages = {950-962},
	abstract = {Summary Odor perception allows animals to distinguish odors,\&nbsp;recognize the same odor across concentrations, and\&nbsp;determine concentration changes. How the activity patterns of primary olfactory receptor neurons (ORNs), at the individual and population levels, facilitate distinguishing these functions remains poorly understood. Here, we interrogate the complete ORN population of the Drosophila larva across a broadly sampled panel of odorants at varying concentrations. We find that the activity of each ORN scales with the concentration of any odorant via a\&nbsp;fixed dose-response function with a variable sensitivity. Sensitivities across odorants and ORNs follow a power-law distribution. Much of receptor sensitivity to odorants is accounted for by a single geometrical property of molecular structure. Similarity in the shape of temporal response filters across\&nbsp;odorants and ORNs extend these relationships to\&nbsp;fluctuating environments. These results uncover shared individual- and population-level patterns that together lend structure to support odor perceptions.},
	keywords = {calcium imaging, combinatorial olfactory code, dose response relationship, Microfluidics, molecular recognition, Olfactory Receptor Neurons, power lab distribution, receptor sensitivity, temporal filter},
	issn = {0896-6273},
	doi = {https://doi.org/10.1016/j.neuron.2018.12.030},
	url = {http://www.sciencedirect.com/science/article/pii/S0896627318311504},
	author = {Si, Guangwei and Jessleen K. Kanwal and Hu, Yu and Christopher J. Tabone and Baron, Jacob and Berck, Matthew and Vignoud, Gaetan and Aravinthan D. T. Samuel}
}
@article {10.3389/fncir.2018.00094,
	title = {A Pipeline for Volume Electron Microscopy of the Caenorhabditis elegans Nervous System},
	journal = {Frontiers in Neural Circuits},
	volume = {12},
	year = {2018},
	pages = {94},
	abstract = {The {\textquotedblleft}connectome,{\textquotedblright} a comprehensive wiring diagram of synaptic connectivity, is achieved through volume electron microscopy (vEM) analysis of an entire nervous system and all associated non-neuronal tissues. White et al. (1986) pioneered the fully manual reconstruction of a connectome using Caenorhabditis elegans. Recent advances in vEM allow mapping new C. elegans connectomes with increased throughput, and reduced subjectivity. Current vEM studies aim to not only fill the remaining gaps in the original connectome, but also address fundamental questions including how the connectome changes during development, the nature of individuality, sexual dimorphism, and how genetic and environmental factors regulate connectivity. Here we describe our current vEM pipeline and projected improvements for the study of the C. elegans nervous system and beyond.},
	issn = {1662-5110},
	doi = {10.3389/fncir.2018.00094},
	url = {https://www.frontiersin.org/article/10.3389/fncir.2018.00094},
	author = {Ben Mulcahy and Witvliet, Daniel and Douglas Holmyard and James Mitchell and Chisholm, Andrew D. and Meirovitch, Yaron and Aravinthan D. T. Samuel and Mei Zhen}
}
@article {Humberg2018,
	title = {Dedicated photoreceptor pathways in Drosophila larvae mediate navigation by processing either spatial or temporal cues},
	journal = {Nature Communications},
	volume = {9},
	number = {1},
	year = {2018},
	pages = {1260},
	abstract = {To integrate changing environmental cues with high spatial and temporal resolution is critical for animals to orient themselves. Drosophila larvae show an effective motor program to navigate away from light sources. How the larval visual circuit processes light stimuli to control navigational decision remains unknown. The larval visual system is composed of two sensory input channels, Rhodopsin5 (Rh5) and Rhodopsin6 (Rh6) expressing photoreceptors (PRs). We here characterize how spatial and temporal information are used to control navigation. Rh6-PRs are required to perceive temporal changes of light intensity during head casts, while Rh5-PRs are required to control behaviors that allow navigation in response to spatial cues. We characterize how distinct behaviors are modulated and identify parallel acting and converging features of the visual circuit. Functional features of the larval visual circuit highlight the principle of how early in a sensory circuit distinct behaviors may be computed by partly overlapping sensory pathways.},
	issn = {2041-1723},
	doi = {10.1038/s41467-018-03520-5},
	url = {https://doi.org/10.1038/s41467-018-03520-5},
	author = {Humberg, Tim-Henning and Bruegger, Pascal and Bruno Afonso and Zlatic, Marta and James W Truman and Marc Gershow and Samuel,Aravinthan and Simon G Sprecher}
}
@article {Hawk157958,
	title = {Integration of plasticity mechanisms within a single sensory neuron of C. elegans actuates a memory},
	journal = {Neuron},
	volume = {97},
	number = {2},
	year = {2018},
	pages = {356-367},
	publisher = {Cold Spring Harbor Laboratory},
	abstract = {Neural plasticity, the ability of a neuron to change its cellular properties in response to past experiences, underpins the nervous system{\textquoteright}s capacity to form memories and actuate behaviors. How different plasticity mechanisms act together in vivo and at a cellular level to transform sensory information into behavior is not well understood. Here we show that in the nematode C. elegans two plasticity mechanisms, sensory adaptation and presynaptic plasticity, act within a single cell to encode thermosensory information and actuate a temperature-preference memory. Sensory adaptation enables the primary thermosensory neuron, AFD, to adjust the temperature range of its sensitivity to the local environment, thereby optimizing its ability to detect temperature fluctuations associated with migration. Presynaptic plasticity transforms this thermosensory information into a behavioral preference by gating synaptic communication between sensory neuron AFD and its postsynaptic partner, AIY. The gating of synaptic communication is regulated at AFD presynaptic sites by the conserved kinase nPKC epsilon Bypassing or altering AFD presynaptic plasticity predictably changes the learned behavioral preferences without affecting sensory responses. Our findings indicate that two distinct and modular neuroplasticity mechanisms function together within a single sensory neuron to encode multiple components of information required to enact thermotactic behavior. The integration of these plasticity mechanisms result in a single-cell logic system that can both represent sensory stimuli and guide memory-based behavioral preference.},
	doi = {10.1101/157958},
	url = {http://www.cell.com/neuron/fulltext/S0896-6273(17)31174-1},
	author = {Hawk, Josh D. and Calvo, Ana C. and Almoril-Porras, Agustin and Aljobeh, Ahmad and Torruella-Suarez, Maria Luisa and Ren, Ivy and Nathan Cook and Joel Greenwood and Linjiao Luo and Aravinthan D. T. Samuel and Daniel Colon-Ramos}
}
@article {He2018,
	title = {Mechanical regulation of stem-cell differentiation by the stretch-activated Piezo channel},
	journal = {Nature},
	volume = {555},
	number = {7694},
	year = {2018},
	pages = {103-106},
	abstract = {Stem cells of the Drosophila midgut sense mechanical signals in vivo through the stretch-activated ion channel Piezo, which is expressed on previously unidentified enteroendocrine precursor cells.},
	issn = {0028-0836},
	doi = {10.1038/nature25744},
	url = {http://www.nature.com/doifinder/10.1038/nature25744},
	author = {He, Li and Si, Guangwei and Huang, Jiuhong and Aravinthan D. T. Samuel and Perrimon, Norbert}
}
@article {579936,
	title = {Exploratory search during directed navigation in C. elegans and Drosophila larva},
	journal = {eLife},
	volume = {6},
	year = {2017},
	abstract = {Many organisms{\textemdash}from bacteria to nematodes to insect larvae{\textemdash}navigate their environments by biasing random movements. In these organisms, navigation in isotropic environments can be characterized as an essentially diffusive and undirected process. In stimulus gradients, movement decisions are biased to drive directed navigation toward favorable environments. How does directed navigation in a gradient modulate random exploration either parallel or orthogonal to the gradient? Here, we introduce methods originally used for analyzing protein folding trajectories to study the trajectories of the nematode\&nbsp;Caenorhabditis elegans\&nbsp;and the\&nbsp;Drosophila\&nbsp;larva in isotropic environments, as well as in thermal and chemical gradients. We find that the statistics of random exploration in any direction are little affected by directed movement along a stimulus gradient. A key constraint on the behavioral strategies of these organisms appears to be the preservation of their capacity to continuously explore their environments in all directions even while moving toward favorable conditions.},
	url = {https://elifesciences.org/articles/30503},
	author = {Mason Klein and Krivov, Sergei V and Ferrer, Anggie and Linjiao Luo and Aravinthan D T Samuel and Karplus, Martin}
}
@article {370366,
	title = {Contrasting responses within a single neuron class enable sex- specific attraction in C. elegans},
	journal = {Proceedings of the National Academy of Sciences USA},
	volume = {113},
	number = {10},
	year = {2016},
	pages = {E1392{\textendash}E1401},
	abstract = {Animals find mates and food, and avoid predators by navigating to regions within a favorable range of available sensory cues. How are these ranges set and recognized? Here we show that male C. elegans exhibit strong concentration preferences for sex- specific small molecule cues secreted by hermaphrodites, and that these preferences emerge from the collective dynamics of a single male-specific class of neurons, the CEMs. Within a single worm, CEM responses are dissimilar, not determined by anatomical classification and can be excitatory or inhibitory. Response kinetics vary by concentration, suggesting a mechanism for establishing preferences. CEM responses are enhanced in the absence of synaptic transmission, and worms with only one intact CEM show non-preferential attraction to all concentrations of ascaroside for which CEM is the primary sensor, suggesting that synaptic modulation of CEM responses is necessary for establishing preferences. A heterogeneous concentration-dependent sensory representation thus appears to allow a single neural class to set behavioral preferences and recognize ranges of sensory cues.\&nbsp;},
	url = {https://www.pnas.org/content/113/10/E1392},
	author = {Anusha Narayan and Vivek Venkatachalam and Omer Durak and Douglas K Reilly and Neelanjan Bose and Frank Schroeder and Samuel,Aravinthan and Jagan Srinivasan and Paul Sternberg}
}
@article {454806,
	title = {Distinct combinations of variant ionotropic glutamate receptors mediate thermosensation and hygrosensation in Drosophila},
	journal = {eLife},
	volume = {5},
	year = {2016},
	pages = {e17879},
	abstract = {Ionotropic Receptors (IRs) are a large subfamily of variant ionotropicglutamate receptors present across Protostomia. While these receptors are mostextensively studied for their roles in chemosensory detection in insects, recent work has\&nbsp;implicated two family members, IR21a and IR25a, in thermosensation in Drosophila.\&nbsp;Here we characterize one of the most deeply conserved receptors, IR93a, and show\&nbsp;that it is co-expressed and functions with IR21a and IR25a to mediate physiological and\&nbsp;behavioral responses to cool temperatures. IR93a is also co-expressed with IR25a and\&nbsp;a distinct receptor, IR40a, in a discrete population of sensory neurons in the sacculus, a\&nbsp;multi-chambered pocket within the antenna. We demonstrate that this combination of\&nbsp;receptors is important for neuronal responses to dry air and behavioral discrimination of\&nbsp;humidity differences. Our results identify IR93a as a common component of molecularlyand cellularly distinct IR pathways underlying thermosensation and hygrosensation in\&nbsp;insects.\&nbsp;},
	url = {http://biorxiv.org/content/early/2016/05/31/056267.full.pdf+html},
	author = {Zachary A. Knecht and Ana F. Silberling and Ni, Lina and Mason Klein and Budelli, Gonzalo and Rati Bell and Liliane Abuin and Anggie J Ferrer and Aravinthan D. T. Samuel and Richard Benton and Garrity, Paul A.}
}
@article {395861,
	title = {An extrasynaptic GABAergic signal modulates a pattern of forward movement in Caenorhabditis elegans},
	journal = {eLife},
	volume = {5},
	year = {2016},
	pages = {e14197},
	abstract = {As a common neurotransmitter in the nervous system, γ-aminobutyric acid (GABA) modulates locomotory patterns in both vertebrates and invertebrates. However, the signaling mechanisms underlying the behavioral effects of GABAergic modulation are not completely understood. Here, we demonstrate that a GABAergic signal in C. elegans modulates the amplitude of undulatory head bending through extrasynaptic neurotransmission and conserved metabotropic receptors. We show that the GABAergic RME head motor neurons generate undulatory activity patterns that correlate with head bending and the activity of RME causally links with head bending amplitude. The undulatory activity of RME is regulated by a pair of cholinergic head motor neurons SMD, which facilitate head bending, and inhibits SMD to limit head bending. The extrasynaptic neurotransmission between SMD and RME provides a gain control system to set head bending amplitude to a value correlated with optimal efficiency of forward movement.},
	url = {http://dx.doi.org/10.7554/eLife.14197},
	author = {Shen,Yu and Quan Wen and He Liu and Connie Zhong and Qin,Yuqi and Gareth Harris and Taizo Kawano and Wu, Min and Tianqi Xu and Samuel,Aravinthan and Zhang,Yun}
}
@article {365731,
	title = {The Ionotropic Receptors IR21a and IR25a mediate cool sensing in Drosophila},
	journal = {eLife},
	volume = {5},
	year = {2016},
	pages = {e13254},
	abstract = {Animals rely on highly sensitive thermoreceptors to seek out optimal temperatures, but the molecular mechanisms of thermosensing are not well understood. The Dorsal Organ Cool Cells (DOCCs) of the Drosophila larva are a set of exceptionally thermosensitive neurons critical for larval cool avoidance. Here we show that DOCC cool-sensing is mediated by Ionotropic Receptors (IRs), a family of sensory receptors widely studied in invertebrate chemical sensing. We find that two IRs, IR21a and IR25a, are required to mediate DOCC responses to cooling and are required for cool avoidance behavior. Furthermore, we find that ectopic expression of IR21a can confer cool-responsiveness in an Ir25a-dependent manner, suggesting an instructive role for IR21a in thermosensing. Together, these data show that IR family receptors can function together to mediate thermosensation of exquisite sensitivity.},
	url = {http://dx.doi.org/10.7554/eLife.13254},
	author = {Ni, Lina and Mason Klein and Svec, Kathryn and Budelli, Gonzalo and Chang, Elaine and Richard Benton and Aravinthan D. T. Samuel and Garrity, Paul}
}
@article {374196,
	title = {Multimodal stimulus coding by a gustatory sensory neuron in Drosophila larvae},
	journal = {Nature Communications},
	volume = {7},
	year = {2016},
	pages = {10687},
	abstract = {Accurate perception of taste information is crucial for animal survival. In adult Drosophila, gustatory receptor neurons (GRNs) perceive chemical stimuli of one specific gustatory modality associated with a stereotyped behavioural response, such as aversion or attraction. We show that GRNs of Drosophila larvae employ a surprisingly different mode of gustatory information coding. Using a novel method for calcium imaging in the larval gustatory system, we identify a multimodal GRN that responds to chemicals of different taste modalities with opposing valence, such as sweet sucrose and bitter denatonium, reliant on different sensory receptors. This multimodal neuron is essential for bitter compound avoidance, and its artificial activation is sufficient to mediate aversion. However, the neuron is also essential for the integration of taste blends. Our findings support a model for taste coding in larvae, in which distinct receptor proteins mediate different responses within the same, multimodal GRN.\&nbsp;},
	url = {https://www.nature.com/articles/ncomms10687},
	author = {Lena van Giesen and Hernandez-Nunez, Luis and Sophie Delasoie-Baranek and Martino Colombo and Philippe Renaud and Bruggmann, Remy and Richard Benton and Aravinthan D. T. Samuel and Simon Sprecher}
}
@article {483551,
	title = {Neuroendocrine Modulation Sustains the C. elegans Forward Motor State},
	journal = {eLIFE},
	volume = {5},
	year = {2016},
	month = {18 Nov},
	pages = {e19887},
	abstract = {Neuromodulators shape neural circuit dynamics. Combining electron microscopy, genetics, transcriptome profiling, calcium imaging, and optogenetics, we discovered a peptidergic neuron that modulates\&nbsp;C. elegans\&nbsp;motor circuit dynamics. The Six/SO-family homeobox transcription factor UNC-39 governs lineage-specific neurogenesis to give rise to a neuron RID. RID bears the anatomic hallmarks of a specialized endocrine neuron: it harbors near-exclusive dense core vesicles that cluster periodically along the axon, and expresses multiple neuropeptides, including the FMRF-amide-related FLP-14. RID activity increases during forward movement. Ablating RID reduces the sustainability of forward movement, a phenotype partially recapitulated by removing FLP-14. Optogenetic depolarization of RID prolongs forward movement, an effect reduced in the absence of FLP-14. Together, these results establish the role of a neuroendocrine cell RID in sustaining a specific behavioral state in\&nbsp;C. elegans.},
	url = {https://elifesciences.org/content/5/e19887},
	author = {Maria A Lim and Jyothsna Chitturi and Valeriya Laskova and Jun Meng and Daniel Findeis and Anne Wiekenberg and Ben Mulcahy and Linjiao Luo and Yan Li and Yangning Lu and Wesley Hung and Yixin Qu and Chi-Yip Ho and Douglas Holmyard and Ni Ji and Rebecca McWhirter and Aravinthan D T Samuel and David M Miller and Ralf Schnabel and John A Calarco and Mei Zhen}
}
@article {357676,
	title = {Panneuronal Imaging in Roaming C. elegans},
	journal = {Proceedings of the National Academy of Sciences USA},
	volume = {113},
	year = {2016},
	pages = {E1082-1088},
	abstract = {We present an imaging system for pan-neuronal recording in crawling\&nbsp;Caenorhabditis elegans. A spinning disk confocal microscope, modified for automated tracking of the\&nbsp;C. elegans\&nbsp;head ganglia, simultaneously records the activity and position of \~80 neurons that coexpress cytoplasmic calcium indicator GCaMP6s and nuclear localized red fluorescent protein at 10 volumes per second. We developed a behavioral analysis algorithm that maps the movements of the head ganglia to the animal{\textquoteright}s posture and locomotion. Image registration and analysis software automatically assigns an index to each nucleus and calculates the corresponding calcium signal. Neurons with highly stereotyped positions can be associated with unique indexes and subsequently identified using an atlas of the worm nervous system. To test our system, we analyzed the brainwide activity patterns of moving worms subjected to thermosensory inputs. We demonstrate that our setup is able to uncover representations of sensory input and motor output of individual neurons from brainwide dynamics. Our imaging setup and analysis pipeline should facilitate mapping circuits for sensory to motor transformation in transparent behaving animals such as\&nbsp;C. elegans\&nbsp;and\&nbsp;Drosophila\&nbsp;larva.},
	url = {http://www.pnas.org/content/early/2015/12/23/1507109113.abstract},
	author = {Vivek Venkatachalam and Ni Ji and Xian Wang and Christopher Clark and James Mitchell and Mason Klein and Christopher Tabone and Jeremy Florman and Hongfei Ji and Joel Greenwood and Andrew Chisholm and Jagan Srinivasan and Mark Alkema and Mei Zhen and Samuel,Aravinthan}
}
@article {364636,
	title = {The wiring diagram of a glomerular olfactory system},
	journal = {eLife},
	volume = {5},
	year = {2016},
	pages = {e14859},
	abstract = {The sense of smell enables animals to detect and react to long-distance cues according to internalized valences. Odors evoke responses from olfactory receptor neurons (ORNs), whose activities are integrated and processed in olfactory glomeruli and then relayed by projection neurons (PNs) to higher brain centers. The wiring diagram with synaptic resolution, which is unknown for any glomerular olfactory system, would enable the formulation of circuit function hypotheses to explain physiological and behavioral observations. Here, we have mapped with electron microscopy the complete wiring diagram of the left and right antennal lobes of Drosophila larva, an olfactory neuropil similar to the vertebrate olfactory bulb. We found two parallel circuits processing ORN inputs. First, a canonical circuit that consists of uniglomerular PNs that relay gain-controlled ORN inputs to the learning and memory center (mushroom body) and the center for innate behaviors (lateral horn). Second, a novel circuit where multiglomerular PNs and hierarchically structured local neurons (LNs) extract complex features from odor space and relay them to multiple brain areas. We found two types of panglomerular inhibitory LNs: one primarily providing presynaptic inhibition (onto ORNs) and another also providing postsynaptic inhibition (onto PNs), indicating that these two functionally different types of inhibition are susceptible to independent modulation. The wiring diagram revealed an LN circuit that putatively implements a bistable gain control mechanism, which either computes odor saliency through panglomerular inhibition, or allows a subset of glomeruli to respond to faint aversive odors in the presence of strong appetitive odor concentrations. This switch between operational modes is regulated by both neuromodulatory neurons and non-olfactory sensory neurons. Descending neurons from higher brain areas further indicate the context-dependent nature of early olfactory processing. The complete wiring diagram of the first olfactory neuropil of a genetically tractable organism will support detailed experimental and theoretical studies of circuit function towards bridging the gap between circuits and behavior.},
	url = {https://elifesciences.org/content/5/e14859},
	author = {Berck, Matthew and Khandelwal, Avinash and Lindsey Claus and Hernandez-Nunez, Luis and Si, Guangwei and Christopher Tabone and Li, Feng and Truman, James and Fetter, Richard and Louis,Matthieu and Samuel,Aravinthan and Cardona, Albert}
}
@article {https://doi.org/10.1111/evo.12813,
	title = {Variability in thermal and phototactic preferences in Drosophila may reflect an adaptive bet-hedging strategy},
	journal = {Evolution},
	volume = {69},
	number = {12},
	year = {2015},
	pages = {3171-3185},
	abstract = {Organisms use various strategies to cope with fluctuating environmental conditions. In diversified bet-hedging, a single genotype exhibits phenotypic heterogeneity with the expectation that some individuals will survive transient selective pressures. To date, empirical evidence for bet-hedging is scarce. Here, we observe that individual Drosophila melanogaster flies exhibit striking variation in light- and temperature-preference behaviors. With a modeling approach that combines real world weather and climate data to simulate temperature preference-dependent survival and reproduction, we find that a bet-hedging strategy may underlie the observed interindividual behavioral diversity. Specifically, bet-hedging outcompetes strategies in which individual thermal preferences are heritable. Animals employing bet-hedging refrain from adapting to the coolness of spring with increased warm-seeking that inevitably becomes counterproductive in the hot summer. This strategy is particularly valuable when mean seasonal temperatures are typical, or when there is considerable fluctuation in temperature within the season. The model predicts, and we experimentally verify, that the behaviors of individual flies are not heritable. Finally, we model the effects of historical weather data, climate change, and geographic seasonal variation on the optimal strategies underlying behavioral variation between individuals, characterizing the regimes in which bet-hedging is advantageous.},
	keywords = {Evolutionary strategy, heritability, Personality, phototaxis, thermotaxis, variation},
	doi = {https://doi.org/10.1111/evo.12813},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/evo.12813},
	author = {Kain, Jamey S. and Sarah Zhang and Akhund-Zade, Jamilla and Aravinthan D. T. Samuel and Mason Klein and de Bivort, Benjamin L.}
}
@article {doi:10.1098/rstb.2014.0212,
	title = {Illuminating neural circuits and behaviour in Caenorhabditis elegans with optogenetics},
	journal = {Philosophical Transactions of the Royal Society B: Biological Sciences},
	volume = {370},
	number = {1677},
	year = {2015},
	pages = {20140212},
	abstract = {The development of optogenetics, a family of methods for using light to control neural activity via light-sensitive proteins, has provided a powerful new set of tools for neurobiology. These techniques have been particularly fruitful for dissecting neural circuits and behaviour in the compact and transparent roundworm Caenorhabditis elegans. Researchers have used optogenetic reagents to manipulate numerous excitable cell types in the worm, from sensory neurons, to interneurons, to motor neurons and muscles. Here, we show how optogenetics applied to this transparent roundworm has contributed to our understanding of neural circuits.},
	doi = {10.1098/rstb.2014.0212},
	url = {https://royalsocietypublishing.org/doi/abs/10.1098/rstb.2014.0212},
	author = {Fang-Yen,Christopher and Mark J. Alkema and Aravinthan D. T. Samuel}
}
@article {253641,
	title = {C. elegans locomotion: small circuits, complex functions},
	journal = {Current Opinion in Neurobiology},
	volume = {33},
	year = {2015},
	pages = {117-126},
	abstract = {With 302 neurons in the adult Caenorhabditis elegans nervous system, it should be possible to build models of complex behaviors spanning sensory input to motor output. The logic of the motor circuit is an essential component of such models. Advances in physiological, anatomical, and neurogenetic analysis are revealing a surprisingly complex signaling network in the worm{\textquoteright}s small motor circuit. We are progressing towards a systems level dissection of the network of premotor interneurons, motor neurons, and muscle cells that move the animal forward and backward in its environment.},
	url = {http://dx.doi.org/10.1016/j.conb.2015.03.009},
	author = {Mei Zhen and Aravinthan D T Samuel}
}
@article {251286,
	title = {Reverse-correlation analysis of navigation dynamics in Drosophila larva using optogenetics},
	journal = {eLife},
	volume = {4},
	year = {2015},
	month = {2015},
	pages = {9},
	abstract = {Neural circuits for behavior transform sensory inputs into motor outputs in patterns with strategic value. Determining how neurons along a sensorimotor circuit contribute to this transformation is central to understanding behavior. To do this, a quantitative framework to describe behavioral dynamics is needed. Here, we built a high-throughput optogenetic system for Drosophila larva to quantify the sensorimotor transformations underlying navigational behavior. We express CsChrimson, a red-shifted variant of Channelrhodopsin, in specific chemosensory neurons, and expose large numbers of freely moving animals to random optogenetic activation patterns. We quantify their behavioral responses and use reverse correlation analysis to uncover the linear and static nonlinear components of navigation dynamics as functions of optogenetic activation patterns of specific sensory neurons. We find that linear-nonlinear (LN) models accurately predict navigational decision-making for different optogenetic activation waveforms. We use our method to establish the valence and dynamics of navigation driven by optogenetic activation of different combinations of bitter sensing gustatory neurons. Our method captures the dynamics of optogenetically-induced behavior in compact, quantitative transformations that can be used to characterize circuits for sensorimotor processing and their contribution to navigational decision-making.},
	url = {http://dx.doi.org/10.7554/eLife.06225},
	author = {Hernandez-Nunez, Luis and Jonas Belina and Mason Klein and Si, Guangwei and Lindsey Claus and John R. Carlson and Aravinthan D T Samuel}
}
@article {223466,
	title = {Sensory determinants of behavioral dynamics in Drosophila thermotaxis},
	journal = {Proceedings of the National Academy of Sciences USA},
	volume = {112},
	number = {2},
	year = {2015},
	pages = {E220-229},
	abstract = {Complex animal behaviors are built from dynamical relationships between sensory inputs, neuronal activity, and motor outputs in patterns with strategic value. Connecting these patterns illuminates how nervous systems compute behavior. Here, we study Drosophila larva navigation up temperature gradients towards preferred temperatures (positive thermotaxis). By tracking the movements of animals responding to fixed spatial temperature gradients or random temperature fluctuations, we calculate the sensitivity and dynamics of the conversion of thermosensory inputs into motor responses. We discover three thermosensory neurons in each dorsal organ ganglion (DOG) that are required for positive thermotaxis. Random optogenetic stimulation of the DOG thermosensory neurons evokes behavioral patterns that mimic the response to temperature variations. \&nbsp;In vivo calcium and voltage imaging reveals that the DOG thermosensory neurons exhibit activity patterns with sensitivity and dynamics matched to the behavioral response. Temporal processing of temperature variations carried out by the DOG thermosensory neurons emerges in distinct motor responses during thermotaxis.},
	url = {http://www.pnas.org/content/112/2/E220},
	author = {Mason Klein and Bruno Afonso and Vonner, Ashley J. and Hernandez-Nunez, Luis and Berck, Matthew E. and Tabone, Christopher J and Elizabeth A Kane and Pieribone, Vincent A. and Nitabach, Michael N. and Cardona, Albert and Zlatic, Marta and Simon G Sprecher and Marc Gershow and Garrity, Paul A. and Aravinthan D T Samuel}
}
@article {678936,
	title = {Thermotaxis navigation behavior},
	journal = {WormBook : the online review of C. elegans biology},
	year = {2014},
	pages = {1-10},
	abstract = {This chapter describes four different protocols used to assay thermotaxis navigation behavior of single, or populations of, C. elegans hermaphrodites on spatial thermal gradients within the physiological temperature range (15-25{\textdegree}C). A method to assay avoidance of noxious temperatures is also described.},
	url = {http://www.wormbook.org/chapters/www_thermonav/thermonav.html},
	author = {Miriam B. Goodman and Mason Klein and Samuel Lasse and Linjiao Luo and Ikue Mori and Aravi Samuel and Piali Sengupta and Wang, Dong}
}
@article {144606,
	title = {Bidirectional thermotaxis in Caenorhabditis elegans is mediated by distinct sensorimotor strategies driven by the AFD thermosensory neurons},
	journal = {Proceedings of the National Academy of Sciences USA},
	volume = {111},
	year = {2014},
	pages = {2776-2781},
	abstract = {The nematode Caenorhabditis elegans navigates toward a pre- ferred temperature setpoint (Ts) determined by long-term temper- ature exposure. During thermotaxis, the worm migrates down temperature gradients at temperatures above Ts (negative ther- motaxis) and performs isothermal tracking near Ts. Under some conditions, the worm migrates up temperature gradients below Ts (positive thermotaxis). Here, we analyze positive and negative thermotaxis toward Ts to study the role of specific neurons that have been proposed to be involved in thermotaxis using genetic ablation, behavioral tracking, and calcium imaging. We find differ- ences in the strategies for positive and negative thermotaxis. Neg- ative thermotaxis is achieved through biasing the frequency of reorientation maneuvers (turns and reversal turns) and biasing the direction of reorientation maneuvers toward colder temper- atures. Positive thermotaxis, in contrast, biases only the direction of reorientation maneuvers toward warmer temperatures. We find that the AFD thermosensory neuron drives both positive and negative thermotaxis. The AIY interneuron, which is postsyn- aptic to AFD, may mediate the switch from negative to positive thermotaxis below Ts. We propose that multiple thermotactic behaviors, each defined by a distinct set of sensorimotor trans- formations, emanate from the AFD thermosensory neurons. AFD learns and stores the memory of preferred temperatures, detects temperature gradients, and drives the appropriate thermotactic behavior in each temperature regime by the flexible use of downstream circuits.},
	url = {https://www.pnas.org/content/111/7/2776},
	author = {Linjiao Luo and Nathan Cook and Vivek Venkatachalam and Luis Martinez-Velazquez and Xiaodong Zhang and Ana Calvo and Josh Hawk and Bronwyn MacInnis and Michelle Frank and Jia Hong Ray Ng and Mason Klein and Marc Gershow and Marc Hammarlund and Miriam Goodman and Daniel Colon-Ramos and Zhang,Yun and Aravinthan D T Samuel}
}
@article {164126,
	title = {Dynamic encoding of perception, memory and movement in a C. elegans chemotaxis circuit},
	journal = {Neuron},
	volume = {82},
	year = {2014},
	pages = {1115-1128},
	abstract = {Brain circuits endow behavioral flexibility. Here, we study circuits encoding flexible 26 chemotaxis in C. elegans, where the animal navigates up or down NaCl gradients (positive or negative chemotaxis) to reach the salt concentration of previous growth (the setpoint). The ASER sensory neuron mediates positive and negative chemotaxis by regulating the frequency and direction of reorientation movements in response to salt gradients. Both salt gradients and setpoint memory are encoded in ASER temporal activity patterns. Distinct temporal activity patterns in interneurons immediately downstream of ASER encode chemotactic movement decisions. Different interneuron combinations regulate positive vs. negative chemotaxis. We conclude that sensorimotor pathways are segregated immediately after the primary sensory neuron in the chemotaxis circuit, and sensory representation is rapidly transformed to motor representation at the first interneuron layer. Our study reveals compact encoding of perception, memory, and locomotion in an experience dependent navigational behavior in C. elegans.},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0896627314003961},
	author = {Linjiao Luo and Quan Wen and Jing Ren and Hendricks,Michael and Marc Gershow and Qin,Yuqi and Joel Greenwood and Edward Soucy and Mason Klein and Heidi Smith-Parker and Ana Calvo and Daniel Colon-Ramos and Samuel,Aravinthan and Zhang,Yun}
}
@article {81191,
	title = {Defining specificity determinants of cyclic GMP-mediated gustatory sensory transduction in Caenorhabditis elegans},
	journal = {Genetics},
	volume = {194},
	number = {4},
	year = {2013},
	pages = {885-901},
	abstract = {Cyclic guanosine monophosphate (cGMP) is a key secondary messenger used in signal transduction in various types of sensory neurons. The importance of cGMP in the ASE gustatory receptor neurons of the nematode\&nbsp;Caenorhabditis elegans\&nbsp;was deduced by the observation that multiple receptor-type guanylyl cyclases (rGCs), encoded by the\&nbsp;gcygenes, and two presently known cyclic nucleotide-gated ion channel subunits, encoded by the\&nbsp;tax-2\&nbsp;and\&nbsp;tax-4\&nbsp;genes, are essential for ASE-mediated gustatory behavior. We describe here specific mechanistic features of cGMP-mediated signal transduction in the ASE neurons. First, we assess the specificity of the sensory functions of individual rGC proteins. We have previously shown that multiple rGC proteins are expressed in a left/right asymmetric manner in the functionally lateralized ASE neurons and are required to sense distinct salt cues. Through domain swap experiments among three different rGC proteins, we show here that the specificity of individual rGC proteins lies in their extracellular domains and not in their intracellular, signal-transducing domains. Furthermore, we find that rGC proteins are also sufficient to confer salt sensory responses to other neurons. Both findings support the hypothesis that rGC proteins are salt receptor proteins. Second, we identify a novel, likely downstream effector of the rGC proteins in gustatory signal transduction, a previously uncharacterized cyclic nucleotide-gated (CNG) ion channel, encoded by the\&nbsp;che-6\&nbsp;locus.\&nbsp;che-6\&nbsp;mutants show defects in gustatory sensory transduction that are similar to defects observed in animals lacking thetax-2\&nbsp;and\&nbsp;tax-4\&nbsp;CNG channels. In contrast, thermosensory signal transduction, which also requires\&nbsp;tax-2\&nbsp;and\&nbsp;tax-4, does not require\&nbsp;che-6, but requires another CNG,\&nbsp;cng-3. We propose that\&nbsp;CHE-6\&nbsp;may form together with two other CNG subunits,\&nbsp;TAX-2\&nbsp;and\&nbsp;TAX-4, a gustatory neuron-specific heteromeric CNG channel complex.},
	url = {https://academic.oup.com/genetics/article/194/4/885/5935327},
	author = {Heidi K. Smith and Linjiao Luo and Damien O{\textquoteright}Halloran and Dagang Guo and Xin-Yun Huang and Aravinthan D. Samuel and Oliver Hobert}
}
@article {129121,
	title = {Rapid and Permanent Neuronal Inactivation In Vivo via Subcellular Generation of Reactive Oxygen with the Use of KillerRed},
	journal = {Cell Reports},
	volume = {5},
	number = {2},
	year = {2013},
	pages = {553-563},
	abstract = {Inactivation of selected neurons in vivo can define their contribution to specific developmental outcomes, circuit functions, and behaviors. Here, we show that the optogenetic tool KillerRed selec- tively, rapidly, and permanently inactivates different classes of neurons in C. elegans in response to a single light stimulus, through the generation of reactive oxygen species (ROS). Ablation scales from individual neurons in single animals to multiple neurons in populations and can be applied to freely behaving animals. Using spatially restricted illumination, we demonstrate that localized KillerRed activation in either the cell body or the axon triggers neuronal degeneration and death of the targeted cell. Finally, targeting KillerRed to mitochondria results in organelle fragmentation without killing the cell, in contrast to the cell death observed when KillerRed is targeted to the plasma membrane. We expect this genetic tool to have wide-ranging applications in studies of circuit function and subcellular responses to ROS.},
	url = {https://academic.oup.com/genetics/article/194/4/885/5935327},
	author = {Daniel C Williams and Rachid El Bejjani and Paulo M Ramirez and Sean Coakley and Shin Ae Kim and Hyewon Lee and Quan Wen and Aravinthan D T Samuel and Hang Lu and Hilliard, Massimo A and Marc Hammarlund}
}
@article {129116,
	title = {Sensorimotor structure of Drosophila larva phototaxis},
	journal = {Proceedings of the National Academy of Sciences},
	volume = {110},
	number = {40},
	year = {2013},
	pages = {E3868-77},
	abstract = {The avoidance of light by fly larvae is a classic paradigm for sensorimotor behavior. Here, we use behavioral assays and video microscopy to quantify the sensorimotor structure of phototaxis using the Drosophila larva. Larval locomotion is composed of sequences of runs (periods of forward movement) that are interrupted by abrupt turns, during which the larva pauses and sweeps its head back and forth, probing local light information to deter- mine the direction of the successive run. All phototactic responses are mediated by the same set of sensorimotor transformations that require temporal processing of sensory inputs. Through functional imaging and genetic inactivation of specific neurons down- stream of the sensory periphery, we have begun to map these sensorimotor circuits into the larval central brain. We find that specific sensorimotor pathways that govern distinct light-evoked responses begin to segregate at the first relay after the photosensory neurons.},
	url = {https://www.pnas.org/content/110/40/E3868},
	author = {Elizabeth A Kane and Marc Gershow and Bruno Afonso and Ivan Larderet and Mason Klein and Ashley R Carter and de Bivort, Benjamin L. and Simon G Sprecher and Aravinthan D T Samuel}
}
@article {129181,
	title = {Shifts in the distribution of mass densities is a signature of caloric restriction in Caenorhabditis elegans},
	journal = {PLoS ONE},
	volume = {8},
	number = {7},
	year = {2013},
	pages = {e69651},
	abstract = {Although the starvation response of the model multicellular organism Caenorhabditis elegans is a subject of much research, there is no convenient phenotypic readout of caloric restriction that can be applicable to large numbers of worms. This paper describes the distribution of mass densities of populations of C. elegans, from larval stages up to day one of adulthood, using isopycnic centrifugation, and finds that density is a convenient, if complex, phenotypic readout in C. elegans. The density of worms in synchronized populations of wildtype N2 C. elegans grown under standard solid-phase culture conditions was normally distributed, with distributions peaked sharply at a mean of 1.091 g/cm3 for L1, L2 and L3 larvae, 1.087 g/cm3 for L4 larvae, 1.081 g/cm3 for newly molted adults, and 1.074 g/cm3 at 24 hours of adulthood. The density of adult worms under starvation stress fell well outside this range, falling to a mean value of 1.054 g/cm3 after eight hours of starvation. This decrease in density correlated with the consumption of stored glycogen in the food-deprived worms. The density of the worms increased when deprived of food for longer durations, corresponding to a shift in the response of the worms: worms sacrifice their bodies by retaining larvae, which consume the adults from within. Density- based screens with the drug Ivermectin on worms cultured on single plates resulted in a clear bimodal (double-peaked) distribution of densities corresponding to drug exposed and non-exposed worms. Thus, measurements of changes in density could be used to conduct screens on the effects of drugs on several populations of worms cultured on single plates.},
	url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0069651},
	author = {Alfonso Reina and Anand B Subramaniam and Laromaine, Anna and Aravinthan D. Samuel and Whitesides, George M.}
}
@article {75651,
	title = {Functional diversity among sensory receptors in a Drosophila olfactory circuit},
	journal = {Proceedings of the National Academy of Sciences USA},
	volume = {110},
	number = {23},
	year = {2013},
	pages = {E2134-43},
	abstract = {
	The ability of an animal to detect, discriminate, and respond to odors depends on the function of its olfactory receptor neurons (ORNs), which in turn depends ultimately on odorant receptors. To understand the diverse mechanisms used by an animal in olfactory coding and computation, it is essential to understand the functional diversity of its odor receptors. The larval olfactory system of Drosophila melanogaster contains 21 ORNs and a comparable number of odorant receptors whose properties have been examined in only a limited way. We systematically screened them with a panel of \~{}500 odorants, yielding \&gt;10,000 receptor-odorant combinations. We identify for each of 19 receptors an odorant that excites it strongly. The responses elicited by each of these odorants are analyzed in detail. The odorants elicited little cross-activation of other receptors at the test concentration; thus, low concentrations of many of these odorants in nature may be signaled by a single ORN. The receptors differed dramatically in sensitivity to their cognate odorants. The responses showed diverse temporal dynamics, with some odorants eliciting supersustained responses. An intriguing question in the field concerns the roles of different ORNs and receptors in driving behavior. We found that the cognate odorants elicited behavioral responses that varied across a broad range. Some odorants elicited strong physiological responses but weak behavioral responses or weak physiological responses but strong behavioral responses.

},
	url = {https://www.pnas.org/content/110/23/E2134},
	author = {Dennis Mathew and Carlotta Martelli and Elizabeth Kelley-Swift and Christopher Brusalis and Marc Gershow and Samuel,Aravinthan and Thierry Emonet and John Carlson}
}
@article {70391,
	title = {Monoaminergic Orchestration of Motor Programs in a Complex C. elegans Behavior},
	journal = {PLoS Biology},
	volume = {11},
	number = {4},
	year = {2013},
	pages = {e1001529},
	url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529},
	author = {J.L. Donnelly and C.M. Clark and A.M. Leifer and J.K. Pirri and M. Haburcak and M.M. Francis and Samuel, A.D.T. and M.J. Alkema}
}
@inbook {40141,
	title = {Chapter 6 - Laser Microsurgery in Caenorhabditis elegans},
	booktitle = {Methods in Cell Biology,},
	volume = {107},
	year = {2012},
	pages = {177-206},
	publisher = {Methods in Cell Biology},
	organization = {Methods in Cell Biology},
	abstract = {Laser killing of cell nuclei has long been a powerful means of examining the roles of individual cells in\&nbsp;C. elegans. Advances in genetics, laser technology, and imaging have further expanded the capabilities and usefulness of laser surgery. Here, we review the implementation and application of currently used methods for target edoptical disruption in\&nbsp;C. elegans.},
	url = {https://www.sciencedirect.com/science/article/pii/B9780123946201000060?via\%3Dihub},
	author = {Fang-Yen, C. and Gabel, C. and Samuel, A. D. and C. Bargmann and L. Avery}
}
@article {40113,
	title = {The core apoptotic executioner proteins CED-3 and CED-4 promote neuronal regeneration in Caenorhabditis elegans},
	journal = {PLoS Biology},
	volume = {10},
	year = {2012},
	pages = {e1001331},
	abstract = {The chemotrophic factor Netrin can simultaneously instruct different neurodevelopmental programs in individual neurons in vivo. How neurons correctly interpret the Netrin signal and undergo the appropriate neurodevelopmental response is not understood. Here we identify MIG-10 isoforms as critical determinants of individual cellular responses to Netrin. We determined that distinct MIG-10 isoforms, varying only in their N-terminal motifs, can localize to specific subcellular domains and are differentially required for discrete neurodevelopmental processes in vivo. We identified MIG-10B as an isoform uniquely capable of localizing to presynaptic regions and instructing synaptic vesicle clustering in response to Netrin. MIG-10B interacts with Abl-interacting protein-1 (ABI-1)/Abi1, a component of the WAVE complex, to organize the actin cytoskeleton at presynaptic sites and instruct vesicle clustering through SNN-1/Synapsin. We identified a motif in the MIG-10B N-terminal domain that is required for its function and localization to presynaptic sites. With this motif, we engineered a dominant-negative MIG-10B construct that disrupts vesicle clustering and animal thermotaxis behavior when expressed in a single neuron in vivo. Our findings indicate that the unique N-terminal domains confer distinct MIG-10 isoforms with unique capabilities to localize to distinct subcellular compartments, organize the actin cytoskeleton at these sites, and instruct distinct Netrin-dependent neurodevelopmental programs.},
	url = {http://www.plosbiology.org/article/info\%3Adoi\%2F10.1371\%2Fjournal.pbio.1001331},
	author = {B. Pinan-Lucarre and Gabel, C. and Hulme, S. E. and S. Shevkopylas and R. Slone and J. Xue and S. Weisberg and G. Whitesides and Samuel, A. D. and M. Driscoll}
}
@article {40112,
	title = {Dopamine signaling sets and maintains a precise rate of locomotion by C. elegans},
	journal = {PLoS ONE},
	volume = {7},
	number = {6},
	year = {2012},
	pages = {e38649},
	abstract = {Dopamine is an important neuromodulator in both vertebrates and invertebrates. We have found that reduced dopamine signaling can cause a distinct abnormality in the behavior of the nematode\&nbsp;C. elegans, which has only eight dopaminergic neurons. Using an automated particle-tracking system for the analysis of\&nbsp;C. elegans\&nbsp;locomotion, we observed that individual wild-type animals made small adjustments to their speed to maintain constant rates of locomotion. By contrast, individual mutant animals defective in the synthesis of dopamine made larger adjustments to their speeds, resulting in large fluctuations in their rates of locomotion. Mutants defective in dopamine signaling also frequently exhibited both abnormally high and abnormally low average speeds. The ability to make small adjustments to speed was restored to these mutants by treatment with dopamine. These behaviors depended on the D2-like dopamine receptor DOP-3 and the G-protein subunit GOA-1. We suggest that\&nbsp;C. elegans\&nbsp;and other animals, including humans, might share mechanisms by which dopamine restricts motor activity levels and coordinates movement.},
	url = {https://doi.org/10.1371/journal.pone.0038649},
	author = {D. Omura and D. Clark and Samuel, A. D. and H.R. Horvitz}
}
@article {40100,
	title = {Synaptic vesicle clustering and axon arborization require distinct MIG-10/Lamellipodin isoforms downstream of Netrin},
	journal = {Genes and Development},
	volume = {26},
	number = {19},
	year = {2012},
	pages = {2206-2221},
	abstract = {The chemotrophic factor Netrin can simultaneously instruct different neurodevelopmental programs in individual neurons in vivo. How neurons correctly interpret the Netrin signal and undergo the appropriate neurodevelopmental response is not understood. Here we identify MIG-10 isoforms as critical determinants of individual cellular responses to Netrin. We determined that distinct MIG-10 isoforms, varying only in their N-terminal motifs, can localize to specific subcellular domains and are differentially required for discrete neurodevelopmental processes in vivo. We identified MIG-10B as an isoform uniquely capable of localizing to presynaptic regions and instructing synaptic vesicle clustering in response to Netrin. MIG-10B interacts with Abl-interacting protein-1 (ABI-1)/Abi1, a component of the WAVE complex, to organize the actin cytoskeleton at presynaptic sites and instruct vesicle clustering through SNN-1/Synapsin. We identified a motif in the MIG-10B N-terminal domain that is required for its function and localization to presynaptic sites. With this motif, we engineered a dominant-negative MIG-10B construct that disrupts vesicle clustering and animal thermotaxis behavior when expressed in a single neuron in vivo. Our findings indicate that the unique N-terminal domains confer distinct MIG-10 isoforms with unique capabilities to localize to distinct subcellular compartments, organize the actin cytoskeleton at these sites, and instruct distinct Netrin-dependent neurodevelopmental programs.},
	url = {https://doi.org/10.1101/gad.193409.112},
	author = {A. Stavoe and Nelson, J. C. and L. Martinez-Velazquez and Klein, M. and Samuel, A. D. and D. Colon-Ramos}
}
@article {40099,
	title = {Proprioceptive Coupling within Motor Neurons Drives C. elegans Forward Locomotion},
	journal = {Neuron},
	volume = {76},
	number = {4},
	year = {2012},
	pages = {750-761},
	abstract = {Locomotion requires coordinated motor activity throughout an animal{\textquoteright}s body. In both vertebrates and invertebrates, chains of coupled central pattern generators (CPGs) are commonly evoked to explain local rhythmic behaviors. In\&nbsp;C.\&nbsp;elegans, we report that proprioception within the motor circuit is responsible for propagating and coordinating rhythmic undulatory waves from head to tail during forward movement. Proprioceptive coupling between adjacent body regions transduces rhythmic movement initiated near the head into bending waves driven along the body by a chain of reflexes. Using optogenetics and calcium imaging to manipulate and monitor motor circuit activity of moving\&nbsp;C.\&nbsp;elegans\&nbsp;held in microfluidic devices, we found that the B-type cholinergic motor neurons transduce the proprioceptive signal. In\&nbsp;C.\&nbsp;elegans, a sensorimotor feedback loop operating within a specific type of motor neuron both drives and organizes body movement.},
	url = {http://www.sciencedirect.com/science/article/pii/S0896627312008057},
	author = {Q. Wen and M.D. Po and E. Hulme and S. Chen and Liu, X. and S. Kwok and M. Gershow and A.M. Leifer and V. Butler and Fang-Yen, C. and T. Kawano and W.R. Schafer and G. Whitesides and M. Wyart and D.B. Chklovskii and M. Zhen and Samuel, A. D.}
}
@article {40119,
	title = {Controlling airborne cues during small animal navigation},
	journal = {Nature Methods},
	volume = {9},
	number = {3},
	year = {2012},
	pages = {290-296},
	abstract = {Small animals such as nematodes and insects analyze airborne chemical cues to infer the direction of favorable and noxious locations. In these animals, the study of navigational behavior evoked by airborne cues has been limited by the difficulty of precisely controlling stimuli. We present a system that can be used to deliver gaseous stimuli in defined spatial and temporal patterns to freely moving small animals. We used this apparatus, in combination with machine-vision algorithms, to assess and quantify navigational decision making of\&nbsp;Drosophila melanogaster\&nbsp;larvae in response to ethyl acetate (a volatile attractant) and carbon dioxide (a gaseous repellant).},
	url = {http://www.nature.com/nmeth/journal/v9/n3/full/nmeth.1853.html},
	author = {M. Gershow and M. Berck and D. Mathew and Luo, L. and E. Kane and J.R. Carlson and Samuel, A. D.}
}
@article {40121,
	title = {Optogenetic control with high spatial and temporal resolution in freely moving C. elegans},
	journal = {Nature Methods},
	volume = {8},
	number = {2},
	year = {2011},
	pages = {147-152},
	abstract = {We present an optogenetic illumination system capable of real-time light delivery with high spatial resolution to specified targets in freely moving\&nbsp;Caenorhabditis elegans. A tracking microscope records the motion of an unrestrained worm expressing channelrhodopsin-2 or halorhodopsin in specific cell types. Image processing software analyzes the worm{\textquoteright}s position in each video frame, rapidly estimates the locations of targeted cells and instructs a digital micromirror device to illuminate targeted cells with laser light of the appropriate wavelengths to stimulate or inhibit activity. Because each cell in an unrestrained worm is a rapidly moving target, our system operates at high speed (\~{}50 frames per second) to provide high spatial resolution (\~{}30 μm). To test the accuracy, flexibility and utility of our system, we performed optogenetic analyses of the worm motor circuit, egg-laying circuit and mechanosensory circuits that have not been possible with previous methods.},
	url = {http://www.nature.com/nmeth/journal/v8/n2/abs/nmeth.1554.html},
	author = {A. Leifer and Fang-Yen, C. and M. Gershow and M. Alkema and Samuel, A. D.}
}
@article {40120,
	title = {Two alternating motor programs drive navigational decision-making in Drosophila larva},
	journal = {PLoS ONE},
	volume = {6},
	number = {8},
	year = {2011},
	pages = {e23180},
	abstract = {
	When placed on a temperature gradient, a\&nbsp;Drosophila\&nbsp;larva navigates away from excessive cold or heat by regulating the size, frequency, and direction of reorientation maneuvers between successive periods of forward movement. Forward movement is driven by peristalsis waves that travel from tail to head. During each reorientation maneuver, the larva pauses and sweeps its head from side to side until it picks a new direction for forward movement. Here, we characterized the motor programs that underlie the initiation, execution, and completion of reorientation maneuvers by measuring body segment dynamics of freely moving larvae with fluorescent muscle fibers as they were exposed to temporal changes in temperature. We find that reorientation maneuvers are characterized by highly stereotyped spatiotemporal patterns of segment dynamics. Reorientation maneuvers are initiated with head sweeping movement driven by asymmetric contraction of a portion of anterior body segments. The larva attains a new direction for forward movement after head sweeping movement by using peristalsis waves that gradually push posterior body segments out of alignment with the tail (i.e., the previous direction of forward movement) into alignment with the head. Thus, reorientation maneuvers during thermotaxis are carried out by two alternating motor programs: (1) peristalsis for driving forward movement and (2) asymmetric contraction of anterior body segments for driving head sweeping movement.

},
	url = {http://www.plosone.org/article/info\%3Adoi\%2F10.1371\%2Fjournal.pone.0023180},
	author = {S. Lahiri and Shen, K. and Klein, M. and A. Tang and E. Kane and M. Gershow and P. Garrity and Samuel, A. D.}
}
@article {40142,
	title = {Running hot and cold: behavioral strategies, neural circuits, and the molecular machinery for thermotaxis in C. elegans and Drosophila},
	journal = {Genes and Development},
	volume = {24},
	year = {2010},
	pages = {2365-2382},
	abstract = {Like other ectotherms, the roundworm\&nbsp;Caenorhabditis elegans\&nbsp;and the fruit fly\&nbsp;Drosophila melanogaster\&nbsp;rely on behavioral strategies to stabilize their body temperature. Both animals use specialized sensory neurons to detect small changes in temperature, and the activity of these thermosensors governs the neural circuits that control migration and accumulation at preferred temperatures. Despite these similarities, the underlying molecular, neuronal, and computational mechanisms responsible for thermotaxis are distinct in these organisms. Here, we discuss the role of thermosensation in the development and survival of\&nbsp;C. elegans\&nbsp;and\&nbsp;Drosophila, and review the behavioral strategies, neuronal circuits, and molecular networks responsible for thermotaxis behavior.},
	url = {http://genesdev.cshlp.org/content/24/21/2365},
	author = {P. Garrity and Goodman, M. and Samuel, A. D. and P. Sengupta}
}
@article {40124,
	title = {Functional Organization of a Neural Network for Aversive Olfactory Learning in Caenorhabditis elegans},
	journal = {Neuron},
	volume = {68},
	number = {6},
	year = {2010},
	pages = {1173-1186},
	abstract = {Many animals use their olfactory systems to learn to avoid dangers, but how neural circuits encode naive and learned olfactory preferences, and switch between those preferences, is poorly understood. Here, we map an olfactory network, from sensory input to motor output, which regulates the learned olfactory aversion of\&nbsp;Caenorhabditis elegans\&nbsp;for the smell of pathogenic bacteria. Naive animals prefer smells of pathogens but animals trained with pathogens lose this attraction. We find that two different neural circuits subserve these preferences, with one required for the naive preference and the other specifically for the learned preference.\&nbsp;Calcium imaging\&nbsp;and behavioral analysis reveal that the naive preference reflects the direct transduction of the activity of olfactory\&nbsp;sensory neurons\&nbsp;into motor response, whereas the learned preference involves modulations to signal transduction to downstream neurons to alter motor response. Thus, two different neural circuits regulate a behavioral switch between naive and learned olfactory preferences.},
	url = {https://www.sciencedirect.com/science/article/pii/S0896627310009414?via\%3Dihub},
	author = {Ha, H. and Hendricks, M. and Shen, Y. and Gabel, C. and Fang-Yen, C. and Qin, Y. and D. Colon-Ramos and Shen, K. and Samuel, A. D. and Y. Zhang}
}
@article {40123,
	title = {Biomechanical analysis of gait adaptation in the nematode Caenorhabditis elegans},
	journal = {Proceedings of the National Academy of Sciences USA},
	volume = {107},
	number = {47},
	year = {2010},
	pages = {20323-20328},
	abstract = {To navigate different environments, an animal must be able to adapt its locomotory gait to its physical surroundings. The nematode\&nbsp;Caenorhabditis elegans, between swimming in water and crawling on surfaces, adapts its locomotory gait to surroundings that impose approximately 10,000-fold differences in mechanical resistance. Here we investigate this feat by studying the undulatory movements of\&nbsp;C. elegans\&nbsp;in Newtonian fluids spanning nearly five orders of magnitude in viscosity. In these fluids, the worm undulatory gait varies continuously with changes in external load: As load increases, both wavelength and frequency of undulation decrease. We also quantify the internal viscoelastic properties of the worm{\textquoteright}s body and their role in locomotory dynamics. We incorporate muscle activity, internal load, and external load into a biomechanical model of locomotion and show that (i) muscle power is nearly constant across changes in locomotory gait, and (ii) the onset of gait adaptation occurs as external load becomes comparable to internal load. During the swimming gait, which is evoked by small external loads, muscle power is primarily devoted to bending the worm{\textquoteright}s elastic body. During the crawling gait, evoked by large external loads, comparable muscle power is used to drive the external load and the elastic body. Our results suggest that\&nbsp;C. elegans\&nbsp;locomotory gait continuously adapts to external mechanical load in order to maintain propulsive thrust.},
	url = {https://www.pnas.org/content/107/47/20323},
	author = {Fang-Yen, C. and M. Wyart and Xie, J. and R. Kawai and T. Kodger and S. Chen and Q. Wen and Samuel, A. D.}
}
@article {40122,
	title = {Navigational decision-making in Drosophila thermotaxis},
	journal = {Journal of Neuroscience },
	volume = {30},
	year = {2010},
	pages = {4261-4272},
	abstract = {
	A mechanistic understanding of animal navigation requires quantitative assessment of the sensorimotor strategies used during navigation and quantitative assessment of how these strategies are regulated by cellular sensors. Here, we examine thermotactic behavior of the\&nbsp;Drosophila melanogaster\&nbsp;larva using a tracking microscope to study individual larval movements on defined temperature gradients. We discover that larval thermotaxis involves a larger repertoire of strategies than navigation in smaller organisms such as motile bacteria and\&nbsp;Caenorhabditis elegans. Beyond regulating run length (i.e., biasing a random walk), the\&nbsp;Drosophila melanogaster\&nbsp;larva also regulates the size and direction of turns to achieve and maintain favorable orientations. Thus, the sharp turns in a larva{\textquoteright}s trajectory represent decision points for selecting new directions of forward movement. The larva uses the same strategies to move up temperature gradients during positive thermotaxis and to move down temperature gradients during negative thermotaxis. Disrupting positive thermotaxis by inactivating cold-sensitive neurons in the larva{\textquoteright}s terminal organ weakens all regulation of turning decisions, suggesting that information from one set of temperature sensors is used to regulate all aspects of turning decisions. The\&nbsp;Drosophila melanogaster\&nbsp;larva performs thermotaxis by biasing stochastic turning decisions on the basis of temporal variations in thermosensory input, thereby augmenting the likelihood of heading toward favorable temperatures at all times.

},
	url = {https://www.jneurosci.org/content/30/12/4261},
	author = {Luo, L. and M. Gershow and M. Rosenzweig and Kang, K. and Fang-Yen, C. and Garrity, P. A. and Samuel, A. D.}
}
@article {40127,
	title = {Inexpensive microscopy for introductory laboratory courses},
	journal = {American Journal of Physics},
	volume = {77},
	number = {10},
	year = {2009},
	pages = {931-938},
	abstract = {
	We present an inexpensive apparatus for bright field and\&nbsp;fluorescence microscopy\&nbsp;with video capture, suitable for introductory laboratory courses. Experiments on\&nbsp;Brownian motion\&nbsp;and the\&nbsp;Boltzmann\&nbsp;distribution of suspended particles in a gravitational field are described. The\&nbsp;Boltzmann\&nbsp;constant is measured in three ways, and the results fall within 15\% of the accepted value.

},
	url = {https://aapt.scitation.org/doi/10.1119/1.3153502},
	author = {J. Peidle and C. Stokes and R. Hart and M. Franklin and R. Newburgh and J. Pahk and W. Rueckner and Samuel, A. D.}
}
@article {40126,
	title = {Caenorhabditis elegans: a model system for systems neuroscience},
	journal = {Current Opinion in Neurobiology},
	volume = {19},
	number = {6},
	year = {2009},
	pages = {637-643},
	abstract = {The nematode\&nbsp;Caenorhabditis elegans\&nbsp;is an excellent model organism for a systems-level understanding of neural circuits and behavior. Advances in the quantitative analyses of behavior and neuronal activity, and the development of new technologies to precisely control and monitor the workings of interconnected circuits, now allow investigations into the molecular, cellular, and systems-level strategies that transform sensory inputs into precise behavioral outcomes.},
	url = {https://www.sciencedirect.com/science/article/pii/S0959438809001330?via\%3Dihub},
	author = {P. Sengupta and Samuel, A. D.}
}
@article {40125,
	title = {Two size-selective mechanisms specifically trap bacteria-sized food particles in Caenorhabditis elegans},
	journal = {Proceedings of the National Academy of Sciences USA},
	volume = {106},
	number = {47},
	year = {2009},
	pages = {20093-20096},
	abstract = {Caenorhabditis elegans\&nbsp;is a filter feeder: it draws bacteria suspended in liquid into its pharynx, traps the bacteria, and ejects the liquid. How pharyngeal pumping simultaneously transports and filters food particles has been poorly understood. Here, we use high-speed video microscopy to define the detailed workings of pharyngeal mechanics. The buccal cavity and metastomal flaps regulate the flow of dense bacterial suspensions and exclude excessively large particles from entering the pharynx. A complex sequence of contractions and relaxations transports food particles in two successive trap stages before passage into the terminal bulb and intestine. Filtering occurs at each trap as bacteria are concentrated in the central lumen while fluids are expelled radially through three apical channels. Experiments with microspheres show that the\&nbsp;C. elegans\&nbsp;pharynx, in combination with the buccal cavity, is tuned to specifically catch and transport particles of a size range corresponding to most soil bacteria.},
	url = {https://www.pnas.org/content/106/47/20093},
	author = {Fang-Yen, C. and L. Avery and Samuel, A. D.}
}
@article {ZHANG20081445,
	title = {A Self-Regulating Feed-Forward Circuit Controlling C. elegans Egg-Laying Behavior},
	journal = {Current Biology},
	volume = {18},
	number = {19},
	year = {2008},
	pages = {1445-1455},
	abstract = {Summary Background Egg laying in Caenorhabditis elegans has been well studied at the genetic and behavioral levels. However, the neural basis of egg-laying behavior is still not well understood; in particular, the roles of specific neurons and the functional nature of the synaptic connections in the egg-laying circuit remain uncharacterized. Results We have used in~vivo neuroimaging and laser surgery to address these questions in intact, behaving animals. We have found that the HSN neurons play a central role in driving egg-laying behavior through direct excitation of the vulval muscles and VC motor neurons. The VC neurons play a dual role in the egg-laying circuit, exciting the vulval muscles while feedback-inhibiting the HSNs. Interestingly, the HSNs are active in the absence of synaptic input, suggesting that egg laying may be controlled through modulation of autonomous HSN activity. Indeed, body touch appears to inhibit egg laying, in part by interfering with HSN calcium oscillations. Conclusions The egg-laying motor circuit comprises a simple three-component system combining feed-forward excitation and feedback inhibition. This microcircuit motif is common in the C. elegans nervous system, as well as in the mammalian cortex; thus, understanding its functional properties in C. elegans may provide insight into its computational role in more complex brains.},
	keywords = {MOLNEURO, SYSNEURO},
	issn = {0960-9822},
	doi = {https://doi.org/10.1016/j.cub.2008.08.047},
	url = {https://www.sciencedirect.com/science/article/pii/S0960982208011251},
	author = {Mi Zhang and Samuel H. Chung and Chris Fang-Yen and Caroline Craig and Rex A. Kerr and Hiroshi Suzuki and Aravinthan D. T. Samuel and Eric Mazur and William R. Schafer}
}
@article {doi:10.1063/1.2996827,
	title = {Swimming C. elegans in a wet granular medium},
	journal = {Chaos: An Interdisciplinary Journal of Nonlinear Science},
	volume = {18},
	number = {4},
	year = {2008},
	pages = {041106},
	doi = {10.1063/1.2996827},
	url = {https://doi.org/10.1063/1.2996827},
	author = {Jung, Sunghwan and Lee,Stella and Samuel,Aravinthan}
}
@article {40166,
	title = {Distinct cellular and molecular mechanisms mediate initial axon development and adult-stage axon regeneration in C. elegans},
	journal = {Development},
	volume = {135},
	number = {21},
	year = {2008},
	pages = {1129-1136},
	abstract = {The molecular and cellular mechanisms that allow adult-stage neurons to regenerate following damage are poorly understood. Recently, axons of motoneurons and mechanosensory neurons in adult\&nbsp;C. elegans\&nbsp;were found to regrow after being snipped by femtosecond laser ablation. Here, we explore the molecular determinants of adult-stage axon regeneration using the AVM mechanosensory neurons. The first step in AVM axon development is a pioneer axonal projection from the cell body to the ventral nerve cord. We show that regeneration of the AVM axon to the ventral nerve cord lacks the deterministic precision of initial axon development, requiring competition and pruning of unwanted axon branches. Nevertheless, axons of injured AVM neurons regrow to the ventral nerve cord with over 60\% reliability in adult animals. In addition, in contrast to initial development, axon guidance during regeneration becomes heavily dependent on cytoplasmic protein MIG-10/Lamellipodin but independent of UNC-129/TGF-β repellent and UNC-40/DCC receptor, and axon growth during regeneration becomes heavily dependent on UNC-34/Ena and CED-10/Rac actin regulators. Thus,\&nbsp;C. elegans\&nbsp;may be used as a genetic system to characterize novel cellular and molecular mechanisms underlying adult-stage nervous system regeneration.},
	url = {https://journals.biologists.com/dev/article/135/21/3623/18571/Distinct-cellular-and-molecular-mechanisms-mediate},
	author = {Gabel, C. and F. Antoine and C. Chuang and Samuel, A. D. and Chang, C.}
}
@article {40165,
	title = {Olfactory behavior of swimming C. elegans analyzed by measuring motile responses to temporal variations of odorants},
	journal = {Journal of Neurophysiology},
	volume = {99},
	number = {5},
	year = {2008},
	pages = {2617-2625},
	abstract = {Caenorhabditis elegans\&nbsp;responds to chemical cues using a small number of chemosensory neurons that detect a large variety of molecules in its environment. During chemotaxis,\&nbsp;C. elegans\&nbsp;biases its migration in spatial chemical gradients by lengthening (/shortening) periods of forward movement when it happens to be moving toward (/away) from preferred locations. In classical assays of chemotactic behavior, a group of crawling worms is placed on an agar plate containing a point source of chemical, the group is allowed to navigate for a period of time, and aggregation of worms near the source is quantified. Here we show that swimming worms exhibit acute motile responses to temporal variations of odor in their surrounding environment, allowing our development of an automated assay of chemotactic behavior with single-animal resolution. By placing individual worms in small microdroplets and quantifying their movements as they respond to the addition and removal of odorized airstreams, we show that the sensorimotor phenotypes of swimming worms (wild-type behavior, the effects of certain mutations, and the effects of laser ablation of specific olfactory neurons) are consistent with aggregation phenotypes previously obtained in crawling assays. The microdroplet swimming assay has certain advantages over crawling assays, including flexibility and precision in defining the stimulus waveform and automated quantification of motor response during stimulus presentation. In this study, we use the microdroplet assay to quantify the temporal dynamics of the olfactory response, the sensitivity to odorant concentration, combinations, and gradients, and the contribution of specific olfactory neurons to overall behavior.},
	url = {https://doi.org/10.1152/jn.00053.2008},
	author = {Luo, L. and Gabel, C. and Ha, H. and Y. Zhang and Samuel, A}
}
@article {40162,
	title = {Microfluidics: streamlining discovery in worm biology},
	journal = {Nature Methods},
	volume = {5},
	number = {7},
	year = {2008},
	pages = {589-590},
	abstract = {Advances in the application of microfluidics technology to biological assays using the model organism Caenorhabditis elegans help to automate otherwise time-consuming experiments.},
	url = {https://www.nature.com/articles/nmeth0708-589},
	author = {S. Hulme and S. Shevkopylas and Samuel, A}
}
@article {40158,
	title = {An olfactory neuron responds stochastically to temperature and modulates Caenorhabditis elegans thermotactic behavior},
	journal = {Proceedings of the National Academy of Sciences USA},
	volume = {105},
	number = {31},
	year = {2008},
	pages = {11002-11007},
	abstract = {Caenorhabditis elegans\&nbsp;navigates thermal gradients by using a behavioral strategy that is regulated by a memory of its cultivation temperature (T\&nbsp;c). At temperatures above or around the\&nbsp;T\&nbsp;c, animals respond to temperature changes by modulating the rate of stochastic reorientation events. The bilateral AFD neurons have been implicated as thermosensory neurons, but additional thermosensory neurons are also predicted to play a role in regulating thermotactic behaviors. Here, we show that the AWC olfactory neurons respond to temperature. Unlike AFD neurons, which respond to thermal stimuli with continuous, graded calcium signals, AWC neurons exhibit stochastic calcium events whose frequency is stimulus-correlated in a\&nbsp;T\&nbsp;c-dependent manner. Animals lacking the AWC neurons or with hyperactive AWC neurons exhibit defects in the regulation of reorientation rate in thermotactic behavior. Our observations suggest that the AFD and AWC neurons encode thermal stimuli via distinct strategies to regulate\&nbsp;C. elegans\&nbsp;thermotactic behavior.},
	url = {https://www.pnas.org/content/105/31/11002},
	author = {D. Biron and Wasserman, S. and J. Thomas and Samuel, A. D. and P. Sengupta}
}
@article {40171,
	title = {Short-Term Adaptation and Temporal Processing in the Cryophilic Response of Caenorhabditis elegans},
	journal = {Journal of Neurophysiology},
	volume = {97},
	year = {2007},
	pages = {1903-1910},
	abstract = {When navigating spatial thermal gradients, the nematode\&nbsp;C. elegans\&nbsp;migrates toward colder temperatures until it reaches its previous cultivation temperature, exhibiting cryophilic movement. The strategy for effecting cryophilic movement is the biased random walk:\&nbsp;C. elegans\&nbsp;extends (shortens) periods of forward movement that are directed down (up) spatial thermal gradients by modulating the probability of reorientation. Here, we analyze the temporal sensory processor that enables cryophilic movement by quantifying the movements of individual worms subjected to defined temperature waveforms. We show that step increases in temperature as small as 0.05{\textdegree}C lead to transient increases in the probability of reorientation followed by gradual adaptation to the baseline level; temperature downsteps leads to similar but inverted responses. Short-term adaptation is a general property of sensory systems, allowing organisms to maintain sensitivity to sensory variations over broad operating ranges. During cryophilic movement\&nbsp;C. elegans\&nbsp;also uses the temporal dynamics of its adaptive response to compute the time derivative of gradual temperature variations with exquisite sensitivity. On the basis of the time derivative, the worm determines how it is oriented in spatial thermal gradients during each period of forward movement. We show that the operating range of the cryophilic response extends to lower temperatures in\&nbsp;ttx-3\&nbsp;mutants, which affects the development of the AIY interneurons. We show that the temporal sensory processor for the cryophilic response is affected by mutation in the EAT-4 glutamate vesicular transporter. Regulating the operating range of the cryophilic response and executing the cryophilic response may have separate neural mechanisms.},
	url = {https://doi.org/10.1152/jn.00892.2006},
	author = {D. Clark and Gabel, C. and Lee, T. and Samuel, A}
}
@article {40170,
	title = {Temporal Activity Patterns in Thermosensory Neurons of Freely Moving Caenorhabditis elegans Encode Spatial Thermal Gradients},
	journal = {Journal of Neuroscience},
	volume = {27},
	number = {23},
	year = {2007},
	pages = {6083{\textendash} 6090},
	abstract = {Our understanding of the operation of neurons and neuronal circuits has come primarily from probing their activity in dissected, anesthetized, or restrained animals. However, the behaviorally relevant operation of neurons and neuronal circuits occurs within intact animals as they freely perform behavioral tasks. The small size and transparency of the nematode\&nbsp;Caenorhabditis elegans\&nbsp;make it an ideal system for noninvasive, optical measurements of neuronal activity. Here, we use a high signal-to-noise version of cameleon, a fluorescent calcium-binding protein, to quantify the activity of the AFD thermosensory neuron of individual worms freely navigating spatial thermal gradients. We find that AFD activity is directly coupled to the worm{\textquoteright}s exploratory movements in spatial thermal gradients. We show that the worm is able, in principle, to evaluate and guide its own thermotactic behaviors with respect to ambient spatial thermal gradients by monitoring the activity of this single thermosensory neuron.},
	url = {https://www.jneurosci.org/content/27/23/6083},
	author = {D. Clark and Gabel, C. and H. Gabel and Samuel, A. D.}
}
@article {40169,
	title = {Mechanosensation and mechanical load modulate the locomotory gait of swimming C. elegans},
	journal = {Journal of Experimental Biology},
	volume = {210},
	number = {13},
	year = {2007},
	pages = {2383-2389},
	abstract = {Animals move through their environments by selecting gaits that are adapted to the physical nature of their surroundings. The nematode\&nbsp;Caenorhabditis elegans\&nbsp;swims through fluids or crawls on surfaces by propagating flexural waves along its slender body and offers a unique opportunity for detailed analysis of locomotory gait at multiple levels including kinematics,biomechanics and the molecular and physiological operation of sensory and motor systems. Here, we study the swimming gait of\&nbsp;C. elegans\&nbsp;in viscous fluids in the range 0.05-50 Pa s. We find that the spatial form of the swimming gait does not vary across this range of viscosities and that the temporal frequency of the swimming gait only decreases by about 20\% with every 10-fold increase in viscosity. Thus,\&nbsp;C. elegans\&nbsp;swims in low gear,such that its musculature can deliver mechanical force and power nearly 1000-fold higher than it delivers when swimming in water. We find that mutations that disrupt mechanosensation, or the laser killing of specific touch receptor neurons, increase the temporal frequency of the undulating gait, revealing a novel effect of mechanosensory input in regulating the putative central pattern generator that produces locomotion. The adaptability of locomotory gait in\&nbsp;C. elegans\&nbsp;may be encoded in sensory and motor systems that allow the worm to respond to its own movement in different physical surroundings.},
	url = {https://journals.biologists.com/jeb/article/210/13/2383/16904/Mechanosensation-and-mechanical-load-modulate-the},
	author = {J. Korta and D.A. Clark and Gabel, C.V. and L. Mahadevan and Samuel, A. D.}
}
@article {40168,
	title = {Neural Circuits Mediate Electrosensory Behavior in Caenorhabditis elegans},
	journal = {Journal of Neuroscience},
	volume = {27},
	number = {28},
	year = {2007},
	pages = {7586 {\textendash}7596},
	abstract = {The nematode\&nbsp;Caenorhabditis elegans\&nbsp;deliberately crawls toward the negative pole in an electric field. By quantifying the movements of individual worms navigating electric fields, we show that\&nbsp;C. elegans\&nbsp;prefers to crawl at specific angles to the direction of the electric field in persistent periods of forward movement and that the preferred angle is proportional to field strength.\&nbsp;C. elegans\&nbsp;reorients itself in response to time-varying electric fields by using sudden turns and reversals, standard reorientation maneuvers that\&nbsp;C. elegans\&nbsp;uses during other modes of motile behavior. Mutation or laser ablation that disrupts the structure and function of amphid sensory neurons also disrupts electrosensory behavior. By imaging intracellular calcium dynamics among the amphid sensory neurons of immobilized worms, we show that specific amphid sensory neurons are sensitive to the direction and strength of electric fields. We extend our analysis to the motor level by showing that specific interneurons affect the utilization of sudden turns and reversals during electrosensory steering. Thus, electrosensory behavior may be used as a model system for understanding how sensory inputs are transformed into motor outputs by the\&nbsp;C. elegans\&nbsp;nervous system.},
	url = {https://www.jneurosci.org/content/27/28/7586},
	author = {Gabel, C. and H. Gabel and D. Pavlichin and A. Kao and D. Clark and Samuel, A}
}
@article {40167,
	title = {Temperature and food mediate long-term thermotactic behavioral plasticity by association-independent mechanisms in C. elegans},
	journal = {Journal of Experimental Biology},
	volume = {210},
	number = {22},
	year = {2007},
	pages = {4043-4052},
	abstract = {Thermotactic behavior in the nematode\&nbsp;Caenorhabditis elegansexhibits long-term plasticity. On a spatial thermal gradient,\&nbsp;C. elegans\&nbsp;tracks isotherms near a remembered set-point(TS) corresponding to its previous cultivation temperature. When navigating at temperatures above its set-point(T\&gt;TS),\&nbsp;C. elegans\&nbsp;crawls down spatial thermal gradients towards the\&nbsp;TS\&nbsp;in what is called cryophilic movement. The\&nbsp;TS\&nbsp;retains plasticity in the adult stage and is reset by \~{}4 h of sustained exposure to a new temperature. Long-term plasticity in\&nbsp;C. elegans\&nbsp;thermotactic behavior has been proposed to represent an associative learning of specific temperatures conditioned in the presence or absence of bacterial food. Here,we use quantitative behavioral assays to define the temperature and food-dependent determinants of long-term plasticity in the different modes of thermotactic behavior. Under our experimental conditions, we find that starvation at a specific temperature neither disrupts\&nbsp;TSresetting toward the starvation temperature nor induces learned avoidance of the starvation temperature. We find that prolonged starvation suppresses the cryophilic mode of thermotactic behavior. The\&nbsp;hen-1\&nbsp;and\&nbsp;tax-6\&nbsp;genes have been reported to affect associative learning between temperature and food-dependent cues. Under our experimental conditions,mutation in the\&nbsp;hen-1\&nbsp;gene, which encodes a secreted protein with an LDL receptor motif, does not significantly affect thermotactic behavior or long-term plasticity. Mutation in the\&nbsp;tax-6\&nbsp;calcineurin gene abolishes thermotactic behavior altogether. In summary, we do not find evidence that long-term plasticity requires association between temperature and the presence or absence of bacterial food.},
	url = {https://journals.biologists.com/jeb/article/210/22/4043/17163/Temperature-and-food-mediate-long-term},
	author = {C. Chi and D. Clark and Lee, S. and D. Biron and Luo, L. and Gabel, C. and J. Brown and P. Sengupta and Samuel, A. D.}
}
@conference {679419,
	title = {Femtosecond laser dissection in C. elegans neural circuits},
	booktitle = {Commercial and Biomedical Applications of Ultrafast Lasers VI},
	volume = {6108},
	year = {2006},
	pages = {1 {\textendash} 6},
	publisher = {International Society for Optics and Photonics},
	organization = {International Society for Optics and Photonics},
	abstract = {The nematode\&nbsp;C. elegans, a millimeter-long roundworm, is a well-established model organism for studies of neural development and behavior, however physiological methods to manipulate and monitor the activity of its neural network have lagged behind the development of powerful methods in genetics and molecular biology. The small size and transparency of\&nbsp;C. elegans\&nbsp;make the worm an ideal test-bed for the development of physiological methods derived from optics and microscopy. We present the development and application of a new physiological tool: femtosecond laser dissection, which allows us to selectively ablate segments of individual neural fibers within live\&nbsp;C. elegans. Femtosecond laser dissection provides a scalpel with submicrometer resolution, and we discuss its application in studies of neural growth, regenerative growth, and the neural basis of behavior.},
	keywords = {Dissection, femtosecond laser, Neural networks, Neuroscience, ultrafast laser},
	url = {https://doi.org/10.1117/12.657396},
	author = {Aravinthan D. T. Samuel and Samuel H. Chung and Clark, Damon A. and Gabel, Christopher V. and Chang, Chieh and Murthy, Venkatesh and Eric Mazur},
	editor = {Joseph Neev and Stefan Nolte and Alexander Heisterkamp and Christopher B. Schaffer}
}
@article {40177,
	title = {The role of the AFD neuron in C. elegans thermotaxis analyzed using femtosecond laser ablation},
	journal = {BMC Neuroscience},
	volume = {7},
	year = {2006},
	pages = {30},
	abstract = {
	Background



	Caenorhabditis elegans\&nbsp;actively crawls down thermal gradients until it reaches the temperature of its prior cultivation, exhibiting what is called cryophilic movement. Implicit in the worm{\textquoteright}s performance of cryophilic movement is the ability to detect thermal gradients, and implicit in regulating the performance of cryophilic movement is the ability to compare the current temperature of its surroundings with a stored memory of its cultivation temperature. Several lines of evidence link the AFD sensory neuron to thermotactic behavior, but its precise role is unclear. A current model contends that AFD is part of a thermophilic mechanism for biasing the worm{\textquoteright}s movement up gradients that counterbalances the cryophilic mechanism for biasing its movement down gradients.



	Results



	We used tightly-focused femtosecond laser pulses to dissect the AFD neuronal cell bodies and the AFD sensory dendrites in\&nbsp;C. elegans\&nbsp;to investigate their contribution to cryophilic movement. We establish that femtosecond laser ablation can exhibit submicrometer precision, severing individual sensory dendrites without causing collateral damage. We show that severing the dendrites of sensory neurons in young adult worms permanently abolishes their sensory contribution without functional regeneration. We show that the AFD neuron regulates a mechanism for generating cryophilic bias, but we find no evidence that AFD laser surgery reduces a putative ability to generate thermophilic bias. In addition, although disruption of the AIY interneuron causes worms to exhibit cryophilic bias at all temperatures, we find no evidence that laser killing the AIZ interneuron causes thermophilic bias at any temperature.



	Conclusion



	We conclude that laser surgical analysis of the neural circuit for thermotaxis does not support a model in which AFD opposes cryophilic bias by generating thermophilic bias. Our data supports a model in which the AFD neuron gates a mechanism for generating cryophilic bias.

},
	url = {https://doi.org/10.1186/1471-2202-7-30},
	author = {S. Chung and D. Clark and Gabel, C. and E Mazur and Samuel, A}
}
@article {40176,
	title = {The AFD Sensory Neurons Encode Multiple Functions Underlying Thermotactic Behavior in Caenorhabditis elegans},
	journal = {Journal of Neuroscience},
	volume = {26},
	number = {28},
	year = {2006},
	pages = {7444-7451},
	abstract = {The thermotactic behaviors of\&nbsp;Caenorhabditis elegans\&nbsp;indicate that its thermosensory system exhibits exquisite temperature sensitivity, long-term plasticity, and the ability to transform thermosensory input into different patterns of motor output. Here, we study the physiological role of the AFD thermosensory neurons by quantifying intracellular calcium dynamics in response to defined temperature stimuli. We demonstrate that short-term adaptation allows AFD to sense temperature changes as small as 0.05{\textdegree}C over temperature ranges as wide as 10{\textdegree}C. We show that a bidirectional thermosensory response (increasing temperature raises and decreasing temperature lowers the level of intracellular calcium in AFD) allows the AFD neurons to phase-lock their calcium dynamics to oscillatory thermosensory inputs. By analyzing the thermosensory response of AFD dendrites severed from their cell bodies by femtosecond laser ablation, we show that long-term plasticity is encoded as shifts in the operating range of a putative thermoreceptor(s) in the AFD sensory endings. Finally, we demonstrate that AFD activity is directly coupled to stimulation of its postsynaptic partner AIY. These observations indicate that many functions underlying thermotactic behavior are properties of one sensory neuronal type. Encoding multiple functions in individual sensory neurons may enable\&nbsp;C. elegans\&nbsp;to perform complex behaviors with simple neuronal circuits.},
	url = {https://www.jneurosci.org/content/26/28/7444},
	author = {D. Clark and D. Biron and P. Sengupta and Samuel, A}
}
@article {40175,
	title = {A diacylglycerol kinase modulates long-term thermotactic behavioral plasticity in C. elegans},
	journal = {Nature Neuroscience},
	volume = {9},
	number = {12},
	year = {2006},
	pages = {1499-1505},
	abstract = {A memory of prior thermal experience governs\&nbsp;Caenorhabditis elegans\&nbsp;thermotactic behavior. On a spatial thermal gradient,\&nbsp;C. elegans\&nbsp;tracks isotherms near a remembered temperature we call the thermotactic set-point (TS). The\&nbsp;TS\&nbsp;corresponds to the previous cultivation temperature and can be reset by sustained exposure to a new temperature. The mechanisms underlying this behavioral plasticity are unknown, partly because sensory and experience-dependent components of thermotactic behavior have been difficult to separate. Using newly developed quantitative behavioral analyses, we demonstrate that the\&nbsp;TS\&nbsp;represents a weighted average of a worm{\textquoteright}s temperature history. We identify the DGK-3 diacylglycerol kinase as a thermal memory molecule that regulates the rate of\&nbsp;TS\&nbsp;resetting by modulating the temperature range of synaptic output, but not temperature sensitivity, of the AFD thermosensory neurons. These results provide the first mechanistic insight into the basis of experience-dependent plasticity in this complex behavior.},
	url = {https://www.nature.com/articles/nn1796},
	author = {D. Biron and M. Shibuya and Gabel, C. and Wasserman, S. and D. Clark and A. Brown and P. Sengupta and Samuel, A}
}
@article {40173,
	title = {Sensorimotor control during isothermal tracking in Caenorhabditis elegans},
	journal = {Journal of Experimental Biology},
	volume = {209},
	number = {23},
	year = {2006},
	pages = {4652-4662},
	abstract = {In order to purposefully navigate their environments, animals rely on precise coordination between their sensory and motor systems. The integrated performance of circuits for sensorimotor control may be analyzed by quantifying an animal{\textquoteright}s motile behavior in defined sensory environments. Here,we analyze the ability of the nematode\&nbsp;C. elegans\&nbsp;to crawl isothermally in spatial thermal gradients by quantifying the trajectories of individual worms responding to defined spatiotemporal thermal gradients. We show that sensorimotor control during isothermal tracking may be summarized as a strategy in which the worm changes the curvature of its propulsive undulations in response to temperature changes measured at its head. We show that a concise mathematical model for this strategy for sensorimotor control is consistent with the exquisite stability of the worm{\textquoteright}s isothermal alignment in spatial thermal gradients as well as its more complex trajectories in spatiotemporal thermal gradients.},
	url = {https://journals.biologists.com/jeb/article/209/23/4652/16470/Sensorimotor-control-during-isothermal-tracking-in},
	author = {Luo, L. and D. Clark and D. Biron and L. Mahadevan and Samuel, A}
}
@article {40178,
	title = {Sensorimotor integration: locating locomotion in neural circuits},
	journal = {Current Biology},
	volume = {15},
	number = {9},
	year = {2005},
	pages = {R341-R343},
	abstract = {Neural components of the circuits that transform sensory cues into changes in motor activities are largely unknown. Several recent studies have now functionally mapped the sensorimotor circuits responsible for locomotion behaviors under defined environmental conditions in the nematode Caenorhabditis elegans.},
	url = {https://www.sciencedirect.com/science/article/pii/S0960982205004215?via\%3Dihub},
	author = {Samuel, A and P. Sengupta}
}
@article {40180,
	title = {Identification of Thermosensory and Olfactory Neuron-Specific Genes via Expression Profiling of Single Neuron Types},
	journal = {Current Biology},
	volume = {14},
	number = {24},
	year = {2004},
	pages = {2245-2251},
	abstract = {Most\&nbsp;C. elegans\&nbsp;sensory neuron\&nbsp;types consist of a single bilateral pair of neurons, and respond to a unique set of\&nbsp;sensory stimuli. Although genes required for the development and function of individual sensory neuron types have been identified in\&nbsp;forward genetic\&nbsp;screens, these approaches are unlikely to identify genes that when mutated result in subtle or pleiotropic phenotypes. Here, we describe a complementary approach to identify sensory neuron type-specific genes via microarray analysis using RNA from sorted AWB olfactory and AFD thermosensory neurons. The expression patterns of subsets of these genes were further verified in vivo. Genes identified by this analysis encode 7-transmembrane receptors, kinases, and nuclear factors including\&nbsp;dac-1, which encodes a homolog of the highly conserved\&nbsp;Dachshund\&nbsp;protein\&nbsp;[1].\&nbsp;dac-1\&nbsp;is expressed in a subset of sensory neurons including the AFD neurons and is regulated by the TTX-1 OTX\&nbsp;homeodomain protein\&nbsp;[2]. On thermal gradients,\&nbsp;dac-1\&nbsp;mutants fail to suppress a cryophilic drive but continue to track isotherms at the cultivation temperature, representing the first genetic separation of these AFD-mediated behaviors. Expression profiling of single neuron types provides a rapid, powerful, and unbiased method for identifying neuron-specific genes whose functions can then be investigated in vivo.},
	url = {https://www.sciencedirect.com/science/article/pii/S0960982204009662?via\%3Dihub},
	author = {M. Colosimo and A. Brown and S. Mukhopadhyay and Gabel, C. and A. Lanjuin and Samuel, A and P. Sengupta}
}
@article {Samuel373,
	title = {Synaptic Activity of the AFD Neuron inCaenorhabditis elegans Correlates with Thermotactic Memory},
	journal = {Journal of Neuroscience},
	volume = {23},
	number = {2},
	year = {2003},
	pages = {373{\textendash}376},
	publisher = {Society for Neuroscience},
	abstract = {Thermotactic behavior in Caenorhabditis elegans is sensitive to both a worm{\textquoteright}s ambient temperature (Tamb) and its memory of the temperature of its cultivation (Tcult). The AFD neuron is part of a neural circuit that underlies thermotactic behavior. By monitoring the fluorescence of pH-sensitive green fluorescent protein localized to synaptic vesicles, we measured the rate of the synaptic release of AFD in worms cultivated at temperatures between 15 and 25{\textdegree}C, and subjected to fixed, ambient temperatures in the same range. We found that the rate of AFD synaptic release is high if either Tamb \&gt;Tcult orTamb \&lt;Tcult, but AFD synaptic release is low if Tamb ≅Tcult. This suggests that AFD encodes a direct comparison between Tamb andTcult.},
	issn = {0270-6474},
	doi = {10.1523/JNEUROSCI.23-02-00373.2003},
	url = {https://www.jneurosci.org/content/23/2/373},
	author = {Aravinthan D. T. Samuel and Silva, Ruwan A. and Murthy, Venkatesh N.}
}
@article {679423,
	title = {Calcium dynamics during fertilization in C. elegans},
	journal = {BMC Developmental Biology},
	volume = {1},
	year = {2001},
	pages = {8},
	abstract = {Of the animals typically used to study fertilization-induced calcium dynamics, none is as accessible to genetics and molecular biology as the model organism\&nbsp;Caenorhabditis elegans.\&nbsp;Motivated by the experimental possibilities inherent in using such a well-established model organism, we have characterized fertilization-induced calcium dynamics in\&nbsp;C. elegans.},
	url = {https://bmcdevbiol.biomedcentral.com/articles/10.1186/1471-213X-1-8$\#$citeas},
	author = {Aravinthan D. T. Samuel and Murthy, Venkatesh N. and Michael O. Hengartner}
}
@article {679422,
	title = {Envelope structure of Synechococcus sp. WH8113, a nonflagellated swimming cyanobacterium},
	journal = {BMC Microbiology},
	volume = {1},
	year = {2001},
	pages = {4},
	abstract = {Many bacteria swim by rotating helical flagellar filaments [1]. Waterbury et al. [15] discovered an exception, strains of the cyanobacterium\&nbsp;Synechococcus\&nbsp;that swim without flagella or visible changes in shape. Other species of cyanobacteria glide on surfaces [2,7]. The hypothesis that\&nbsp;Synechococcus\&nbsp;might swim using traveling surface waves [6,13] prompted this investigation.},
	url = {https://bmcmicrobiol.biomedcentral.com/articles/10.1186/1471-2180-1-4$\#$citeas},
	author = {Aravinthan D. T. Samuel and Jennifer D. Peterson and Thomas S. Reese}
}
@article {TURNER1999597,
	title = {Temperature Dependence of Switching of the Bacterial Flagellar Motor by the Protein CheY13DK106YW},
	journal = {Biophysical Journal},
	volume = {77},
	number = {1},
	year = {1999},
	pages = {597-603},
	abstract = {The behavior of the bacterium Escherichia coli is controlled by switching of the flagellar rotary motor between the two rotational states, clockwise (CW) and counterclockwise (CCW). The molecular mechanism for switching remains unknown, but binding of the response regulator CheY-P to the motor component FliM enhances CW rotation. This effect is mimicked by the unphosphorylated double mutant CheY13DK106YW (CheY**). To learn more about switching, we measured the fraction of time that a motor spends in the CW state (the CW bias) at different concentrations of CheY** and at different temperatures. From the CW bias, we computed the standard free energy change of switching. In the absence of CheY, this free energy change is a linear function of temperature (Turner et al., 1996. Biophys. J. 71:2227{\textendash}2233). In the presence of CheY**, it is nonlinear. However, the data can be fit by models in which binding of each molecule of CheY** shifts the difference in free energy between CW and CCW states by a fixed amount. The shift increases linearly from \~{}0.3kT per molecule at 5{\textdegree}C to \~{}0.9kT at 25{\textdegree}C, where k is Boltzmann{\textquoteright}s constant and T is 289 Kelvin (= 16{\textdegree}C). The entropy and enthalpy contributions to this shift are about -0.031kT/{\textdegree}C and 0.10kT, respectively.},
	issn = {0006-3495},
	doi = {https://doi.org/10.1016/S0006-3495(99)76916-X},
	url = {https://www.sciencedirect.com/science/article/pii/S000634959976916X},
	author = {Linda Turner and Aravinthan D. T. Samuel and Alan S. Stern and Berg, Howard C.}
}
@article {Samuel9863,
	title = {Flagellar determinants of bacterial sensitivity to χ-phage},
	journal = {Proceedings of the National Academy of Sciences},
	volume = {96},
	number = {17},
	year = {1999},
	pages = {9863{\textendash}9866},
	publisher = {National Academy of Sciences},
	abstract = {Bacteriophage χ is known to infect motile strains of enteric bacteria by adsorbing randomly along the length of a flagellar filament and then injecting its DNA into the bacterial cell at the filament base. Here, we provide evidence for a {\textquotedblleft}nut and bolt{\textquotedblright} model for translocation of phage along the filament: the tail fiber of χ fits the grooves formed by helical rows of flagellin monomers, and active flagellar rotation forces the phage to follow the grooves as a nut follows the threads of a bolt.},
	issn = {0027-8424},
	doi = {10.1073/pnas.96.17.9863},
	url = {https://www.pnas.org/content/96/17/9863},
	author = {Aravinthan D. T. Samuel and Pitta, Thomas P. and Ryu,William S. and Danese, Paul N. and Edward C.W. Leung and Berg, Howard C.}
}
@article {doi:10.1063/1.869919,
	title = {Tumbling cards},
	journal = {Physics of Fluids},
	volume = {11},
	number = {1},
	year = {1999},
	pages = {1-3},
	abstract = {When a stiff rectangular card is dropped in still air with its long axis horizontal, it often settles into a regular mode of motion; while revolving around its long axis it descends along a path that is inclined to the vertical at a nearly constant angle. We show experimentally that the tumbling frequency\&nbsp;Omega\&nbsp;of a card of length\&nbsp;\(l\),\&nbsp;width\&nbsp;\(w\)\&nbsp;and thickness\&nbsp;\(d\&nbsp;(l>>w>>d)(l>>w>>d)\)\&nbsp;scales as Omega ~ d1/2w-1,\&nbsp;consistent with a simple dimensional argument that balances the drag against gravity.},
	doi = {10.1063/1.869919},
	url = {https://doi.org/10.1063/1.869919},
	author = {L. Mahadevan and Ryu,William S. and Aravinthan D. T. Samuel}
}
@article {679428,
	title = {Fluid {\textquoteleft}rope trick{\textquoteright} investigated },
	journal = {Nature},
	volume = {392},
	number = {140},
	year = {1998},
	abstract = {Buckling instabilities can arise from competition between axial compression and bending in slender objects. These are not restricted to solids, but also occur with fluids with free surfaces1,4, in geophysics5\&nbsp;and in materials processing6. Here we consider a classic demonstration of fluid buckling7.},
	url = {https://www.nature.com/articles/32321},
	author = {L. Mahadevan and Ryu,William S. and Aravinthan D. T. Samuel}
}
@article {679429,
	title = {Statistical kinetics of the bacterial flagellar motor},
	journal = {Physical Review E},
	volume = {55},
	number = {6},
	year = {1997},
	pages = {7801-7804},
	abstract = {The statistical behavior of the bacterial flagellar motor matches that of a Poisson stepper that takes at least 400 steps per revolution. Using this fact, we study the effect of motor stochastics on experiments in which fluorescent motors, initially synchronized by polarization photobleaching, become uncorrelated.},
	url = {https://link.aps.org/doi/10.1103/PhysRevE.55.7801},
	author = {Aravinthan D. T. Samuel and Berg, Howard C.}
}
@article {679433,
	title = {Propulsion of Microorganisms by Surface Distortions},
	journal = {Physical Review Letters},
	volume = {77},
	number = {19},
	year = {1996},
	pages = {4102-4104},
	abstract = {Swimming strategies of microorganisms must conform to the principles of self-propulsion at low Reynolds numbers. Here we relate the translational and rotational speeds to the surface motions of a swimmer and, for spheres, make evident novel constraints on mechanisms for propulsion. The results are applied to a cyanobacterium, an organism whose motile mechanism is unknown, by considering incompressible streaming of the cell surface and oscillatory, tangential surface deformations. Finally, swimming efficiency using tangential motions is related to the surface velocities and a bound on the efficiency is obtained.},
	url = {https://link.aps.org/doi/10.1103/PhysRevLett.77.4102},
	author = {Howard A. Stone and Aravinthan D. T. Samuel}
}
@article {SAMUEL1996918,
	title = {Torque-generating units of the bacterial flagellar motor step independently},
	journal = {Biophysical Journal},
	volume = {71},
	number = {2},
	year = {1996},
	pages = {918-923},
	abstract = {Measurements of the variance in rotation period of tethered cells as a function of mean rotation rate have shown that the flagellar motor of Escherichia coli is a stepping motor. Here, by measurement of the variance in rotation period as a function of the number of active torque-generating units, it is shown that each unit steps independently.},
	issn = {0006-3495},
	doi = {https://doi.org/10.1016/S0006-3495(96)79295-0},
	url = {https://www.sciencedirect.com/science/article/pii/S0006349596792950},
	author = {Samuel, A. D. and Berg, H.C.}
}
@article {Ehlers8340,
	title = {Do cyanobacteria swim using traveling surface waves?},
	journal = {Proceedings of the National Academy of Sciences},
	volume = {93},
	number = {16},
	year = {1996},
	pages = {8340{\textendash}8343},
	publisher = {National Academy of Sciences},
	abstract = {Bacteria that swim without the benefit of flagella might do so by generating longitudinal or transverse surface waves. For example, swimming speeds of order 25 microns/s are expected for a spherical cell propagating longitudinal waves of 0.2 micron length, 0.02 micron amplitude, and 160 microns/s speed. This problem was solved earlier by mathematicians who were interested in the locomotion of ciliates and who considered the undulations of the envelope swept out by ciliary tips. A new solution is given for spheres propagating sinusoidal waveforms rather than Legendre polynomials. The earlier work is reviewed and possible experimental tests are suggested.},
	issn = {0027-8424},
	doi = {10.1073/pnas.93.16.8340},
	url = {https://www.pnas.org/content/93/16/8340},
	author = {Ehlers, K M and Samuel, A. D. and Berg, H. C. and Montgomery, R}
}
@article {Samuel3502,
	title = {Fluctuation analysis of rotational speeds of the bacterial flagellar motor.},
	journal = {Proceedings of the National Academy of Sciences},
	volume = {92},
	number = {8},
	year = {1995},
	pages = {3502{\textendash}3506},
	publisher = {National Academy of Sciences},
	abstract = {We measured the dependence of the variance in the rotation rate of tethered cells of Escherichia coli on the mean rotation rate over a regime in which the motor generates constant torque. This dependence was compared with that of broken motors. In either case, motor torque was augmented with externally applied torque. We show that, in contrast to broken motors, functioning motors in this regime do not freely rotationally diffuse and that the variance measurements are consistent with the predicted values of a stepping mechanism with exponentially distributed waiting times (a Poisson stepper) that steps approximately 400 times per revolution.},
	issn = {0027-8424},
	doi = {10.1073/pnas.92.8.3502},
	url = {https://www.pnas.org/content/92/8/3502},
	author = {Samuel, A. D. and Berg, H. C.}
}
