Person: Gershow, Marc
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Gershow
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Gershow, Marc
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Publication Proprioceptive Coupling within Motor Neurons Drives C. Elegans Forward Locomotion(Elsevier BV, 2012) Wen, Quan; Po, Michelle D.; Hulme, Elizabeth; Chen, Sway; Liu, Xinyu; Kwok, Sen Wai; Gershow, Marc; Leifer, Andrew M.; Butler, Victoria; Fang-Yen, Christopher M.; Kawano, Taizo; Schafer, William R.; Whitesides, George; Wyart, Matthieu; Chklovskii, Dmitri B.; Zhen, Mei; Samuel, AraviLocomotion requires coordinated motor activity throughout an animal’s body. In both vertebrates and invertebrates, chains of coupled central pattern generators (CPGs) are commonly evoked to explain local rhythmic behaviors. In C. 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 C. elegans held in microfluidic devices, we found that the B-type cholinergic motor neurons transduce the proprioceptive signal. In C. elegans, a sensorimotor feedback loop operating within a specific type of motor neuron both drives and organizes body movement.Publication Controlling Airborne Cues to Study Small Animal Navigation(Nature Publishing Group, 2012) Gershow, Marc; Berck, Matthew; Mathew, Dennis; Luo, Linjiao; Kane, Elizabeth; Carlson, John R; Samuel, AraviSmall 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 Drosophila melanogaster larvae in response to ethyl acetate (a volatile attractant) and carbon dioxide (a gaseous repellant).Publication Functional diversity among sensory receptors in a Drosophila olfactory circuit(Proceedings of the National Academy of Sciences, 2013) Mathew, Dennis; Martelli, Carlotta; Kelley-Swift, Elizabeth; Brusalis, Christopher; Gershow, Marc; Samuel, Aravi; Emonet, Thierry; Carlson, John R.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 >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 thefield 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.Publication DNA molecules and configurations in a solid-state nanopore microscope(Nature Publishing Group, 2003) Li, Jiali; Gershow, Marc; Stein, Derek; Brandin, Eric Richard; Golovchenko, JeneA nanometre scale pore in a solid state membrane provides a new way to electronically probe the structure of single linear polymers, including those of biological interest in their native environments. Previous work with biological protein pores wide enough to pass and sense single stranded DNA molecules demonstrates the power of the nanopore approach, but many future tasks and applications call for a robust solid-state pore whose nanometre scale dimensions and properties may be selected, as one selects the lenses of a microscope. Here we demonstrate a solid-state nanopore microscope capable of observing individual molecules of double stranded DNA and their folding behaviour. We discuss extensions of the nanopore microscope concept to alternative probing mechanisms and applications including the study of molecular structure and sequencing.Publication Bidirectional thermotaxis in Caenorhabditis elegans is mediated by distinct sensorimotor strategies driven by the AFD thermosensory neurons(Proceedings of the National Academy of Sciences, 2014) Luo, Linjiao; Cook, N.; Venkatachalam, Vivek; Martinez-Velazquez, L. A.; Zhang, Xiaosong; Calvo, A. C.; Hawk, J.; Macinnis, Bronwyn; Frank, Michelle; Ng, J. H. R.; Klein, Mason; Gershow, Marc; Hammarlund, M.; Goodman, M. B.; Colon-Ramos, D. A.; Zhang, Y.; Samuel, AraviThe nematode Caenorhabditis elegans navigates toward a preferred temperature setpoint (Ts) determined by long-term temperature exposure. During thermotaxis, the worm migrates down temperature gradients at temperatures above Ts (negative thermotaxis) 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 differences in the strategies for positive and negative thermotaxis. Negative thermotaxis is achieved through biasing the frequency of reorientation maneuvers (turns and reversal turns) and biasing the direction of reorientation maneuvers toward colder temperatures. 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 postsynaptic 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 transformations, 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.Publication Sensory determinants of behavioral dynamics in Drosophila thermotaxis(Proceedings of the National Academy of Sciences, 2014) Klein, Mason; Afonso, Bruno; Vonner, Ashley James; Hernandez-Nunez, Luis; Berck, Matthew; Tabone, Christopher; Kane, Elizabeth; Pieribone, Vincent A.; Nitabach, Michael N.; Cardona, Albert; Zlatic, Marta; Sprecher, Simon G.; Gershow, Marc; Garrity, Paul A.; Samuel, AraviComplex 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 toward 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. 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.Publication Recapturing and trapping single molecules with a solid-state nanopore(Nature Publishing Group, 2007) Gershow, Marc; Golovchenko, JeneThe development of solid state nanopores, inspired by their biological counterparts, shows great potential for the study of single macromolecules. Applications such as DNA sequencing and exploration of protein folding will require understanding and control of the dynamics of a molecule’s interaction with the pore, but DNA capture by a solid state nanopore is not well understood. By recapturing individual molecules soon after they pass through a nanopore, we reveal the mechanism by which double stranded DNA enters the pore. Observed recapture rates and times agree with solutions of a drift-diffusion model. Electric forces draw DNA to the pore over micron distances, and, upon arrival at the pore, molecules begin translocation almost immediately. Repeated translocation of the same molecule improves measurement accuracy, offers a way to probe chemical transformations and internal dynamics of macromolecules on sub-millisecond time and sub-micron length scales, and demonstrates the ability to trap, study, and manipulate individual macromolecules in solution.Publication Sensorimotor structure of Drosophila larva phototaxis(Proceedings of the National Academy of Sciences, 2013) Kane, E. A.; Gershow, Marc; Afonso, Bruno; Larderet, I.; Klein, Mason; Carter, A. R.; de Bivort, Benjamin; Sprecher, S. G.; Samuel, AraviThe 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 determine 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 downstream 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.Publication Detecting Single Stranded DNA with a Solid State Nanopore(American Chemical Society (ACS), 2005) Fologea, Daniel; Gershow, Marc; Ledden, Bradley; McNabb, David S.; Golovchenko, Jene; Li, JialiVoltage biased solid-state nanopores are used to detect and characterize individual single stranded DNA molecules of fixed micrometer length by operating a nanopore detector at pH values greater than ∼11.6. The distribution of observed molecular event durations and blockade currents shows that a significant fraction of the events obey a rule of constant event charge deficit (ecd) indicating that they correspond to molecules translocating through the nanopore in a distribution of folded and unfolded configurations. A surprisingly large component is unfolded. The result is an important milestone in developing solid-state nanopores for single molecule sequencing applications.Publication Navigational Decision Making in Drosophila Thermotaxis(Society for Neuroscience, 2010) Luo, Linjiao; Gershow, Marc; Rosenzweig, Mark; Kang, Kyeonglin; Fang-Yen, Christopher M.; Garrity, Paul A,; Samuel, AraviA 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 Drosophila melanogaster 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 Caenorhabditis elegans. Beyond regulating run length (i.e., biasing a random walk), the Drosophila melanogaster larva also regulates the size and direction of turns to achieve and maintain favorable orientations. Thus, the sharp turns in a larva’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’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 Drosophila melanogaster 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.