Cornelia I Bargmann

The Rockefeller University, New York, New York, United States

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Publications (167)2739.86 Total impact

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    ABSTRACT: Random search is a behavioral strategy used by organisms from bacteria to humans to locate food that is randomly distributed and undetectable at a distance. We investigated this behavior in the nematode Caenorhabditis elegans, an organism with a small, well-described nervous system. Here we formulate a mathematical model of random search abstracted from the C. elegans connectome and fit to a large-scale kinematic analysis of C. elegans behavior at submicron resolution. The model predicts behavioral effects of neuronal ablations and genetic perturbations, as well as unexpected aspects of wild type behavior. The predictive success of the model indicates that random search in C. elegans can be understood in terms of a neuronal flip-flop circuit involving reciprocal inhibition between two populations of stochastic neurons. Our findings establish a unified theoretical framework for understanding C. elegans locomotion and a testable neuronal model of random search that can be applied to other organisms.
    Preview · Article · Jan 2016 · eLife Sciences
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    ABSTRACT: Animals have a remarkable ability to track dynamic sensory information. For example, the nematode Caenorhabditis elegans can locate a diacetyl odor source across a 100,000-fold concentration range. Here, we relate neuronal properties, circuit implementation, and behavioral strategies underlying this robust navigation. Diacetyl responses in AWA olfactory neurons are concentration and history dependent; AWA integrates over time at low odor concentrations, but as concentrations rise, it desensitizes rapidly through a process requiring cilia transport. After desensitization, AWA retains sensitivity to small odor increases. The downstream AIA interneuron amplifies weak odor inputs and desensitizes further, resulting in a stereotyped response to odor increases over three orders of magnitude. The AWA-AIA circuit drives asymmetric behavioral responses to odor increases that facilitate gradient climbing. The adaptation-based circuit motif embodied by AWA and AIA shares computational properties with bacterial chemotaxis and the vertebrate retina, each providing a solution for maintaining sensitivity across a dynamic range.
    No preview · Article · Sep 2015 · Cell Reports
  • Cornelia I Bargmann

    No preview · Article · Jul 2015 · JAMA The Journal of the American Medical Association
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    ABSTRACT: The evolution of the field of neuroscience has been propelled by the advent of novel technological capabilities, and the pace at which these capabilities are being developed has accelerated dramatically in the past decade. Capitalizing on this momentum, the United States launched the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative to develop and apply new tools and technologies for revolutionizing our understanding of the brain. In this article, we review the scientific vision for this initiative set forth by the National Institutes of Health and discuss its implications for the future of neuroscience research. Particular emphasis is given to its potential impact on the mapping and study of neural circuits, and how this knowledge will transform our understanding of the complexity of the human brain and its diverse array of behaviours, perceptions, thoughts and emotions.
    Preview · Article · May 2015 · Philosophical Transactions of The Royal Society B Biological Sciences
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    ABSTRACT: We have developed an imaging system for 3D time-lapse polarization microscopy of living biological samples. Polarization imaging reveals the position, alignment and orientation of submicroscopic features in label-free as well as fluorescently labeled specimens. Optical anisotropies are calculated from a series of images where the sample is illuminated by light of different polarization states. Due to the number of images necessary to collect both multiple polarization states and multiple focal planes, 3D polarization imaging is most often prohibitively slow. Our MF-PolScope system employs multifocus optics to form an instantaneous 3D image of up to 25 simultaneous focal-planes. We describe this optical system and show examples of 3D multi-focus polarization imaging of biological samples, including a protein assembly study in budding yeast cells.
    Full-text · Article · Mar 2015 · Optics Express
  • Andrew Gordus · Navin Pokala · Sagi Levy · Steven W Flavell · Cornelia I Bargmann
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    ABSTRACT: Variability is a prominent feature of behavior and is an active element of certain behavioral strategies. To understand how neuronal circuits control variability, we examined the propagation of sensory information in a chemotaxis circuit of C. elegans where discrete sensory inputs can drive a probabilistic behavioral response. Olfactory neurons respond to odor stimuli with rapid and reliable changes in activity, but downstream AIB interneurons respond with a probabilistic delay. The interneuron response to odor depends on the collective activity of multiple neurons-AIB, RIM, and AVA-when the odor stimulus arrives. Certain activity states of the network correlate with reliable responses to odor stimuli. Artificially generating these activity states by modifying neuronal activity increases the reliability of odor responses in interneurons and the reliability of the behavioral response to odor. The integration of sensory information with network states may represent a general mechanism for generating variability in behavior. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Mar 2015 · Cell
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    Cornelia I Bargmann · Jeffrey A Lieberman

    Full-text · Article · Oct 2014 · American Journal of Psychiatry
  • Cornelia I Bargmann · William T Newsome

    No preview · Article · Apr 2014
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    Navin Pokala · Qiang Liu · Andrew Gordus · Cornelia I Bargmann
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    ABSTRACT: Recent progress in neuroscience has been facilitated by tools for neuronal activation and inactivation that are orthogonal to endogenous signaling systems. We describe here a chemical-genetic approach for inducible silencing of Caenorhabditis elegans neurons in intact animals, using the histamine-gated chloride channel HisCl1 from Drosophila and exogenous histamine. Administering histamine to freely moving C. elegans that express HisCl1 transgenes in neurons leads to rapid and potent inhibition of neural activity within minutes, as assessed by behavior, functional calcium imaging, and electrophysiology of neurons expressing HisCl1. C. elegans does not use histamine as an endogenous neurotransmitter, and exogenous histamine has little apparent effect on wild-type C. elegans behavior. HisCl1-histamine silencing of sensory neurons, interneurons, and motor neurons leads to behavioral effects matching their known functions. In addition, the HisCl1-histamine system can be used to titrate the level of neural activity, revealing quantitative relationships between neural activity and behavioral output. We use these methods to dissect escape circuits, define interneurons that regulate locomotion speed (AVA, AIB) and escape-related omega turns (AIB), and demonstrate graded control of reversal length by AVA interneurons and DA/VA motor neurons. The histamine-HisCl1 system is effective, robust, compatible with standard behavioral assays, and easily combined with optogenetic tools, properties that should make it a useful addition to C. elegans neurotechnology.
    Preview · Article · Feb 2014 · Proceedings of the National Academy of Sciences
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    Saul Kato · Yifan Xu · Christine E Cho · L F Abbott · Cornelia I Bargmann
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    ABSTRACT: Animals track fluctuating stimuli over multiple timescales during natural olfactory behaviors. Here, we define mechanisms underlying these computations in Caenorhabditis elegans. By characterizing neuronal calcium responses to rapidly fluctuating odor sequences, we show that sensory neurons reliably track stimulus fluctuations relevant to behavior. AWC olfactory neurons respond to multiple odors with subsecond precision required for chemotaxis, whereas ASH nociceptive neurons integrate noxious cues over several seconds to reach a threshold for avoidance behavior. Each neuron's response to fluctuating stimuli is largely linear and can be described by a biphasic temporal filter and dynamical model. A calcium channel mutation alters temporal filtering and avoidance behaviors initiated by ASH on similar timescales. A sensory G-alpha protein mutation affects temporal filtering in AWC and alters steering behavior in a way that supports an active sensing model for chemotaxis. Thus, temporal features of sensory neurons can be propagated across circuits to specify behavioral dynamics.
    Preview · Article · Jan 2014 · Neuron
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    Elizabeth E Glater · Matthew V Rockman · Cornelia I Bargmann
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    ABSTRACT: The nematode Caenorhabditis elegans can use olfaction to discriminate among different kinds of bacteria, its major food source. We here ask how natural genetic variation contributes to choice behavior, focusing on differences in olfactory preference behavior between two wild-type C. elegans strains. The laboratory strain N2 strongly prefers the odor of Serratia marcescens, a soil bacterium that is pathogenic to C. elegans, to the odor of Escherichia coli, a commonly used laboratory food source. The divergent Hawaiian strain CB4856 has a weaker attraction to Serratia than the N2 strain, and this behavioral difference has a complex genetic basis. At least three QTLs from HW with large effect sizes lead to reduced Serratia preference when introgressed into an N2 genetic background. These loci interact and have epistatic interactions with at least two antagonistic QTLs from HW that increase Serratia preference. The complex genetic architecture of this C. elegans trait is reminiscent of the architecture of mammalian metabolic and behavioral traits.
    Preview · Article · Dec 2013 · G3-Genes Genomes Genetics
  • Johannes Larsch · Donovan Ventimiglia · Cornelia I Bargmann · Dirk R Albrecht
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    ABSTRACT: Neuronal responses to sensory inputs can vary based on genotype, development, experience, or stochastic factors. Existing neuronal recording techniques examine a single animal at a time, limiting understanding of the variability and range of potential responses. To scale up neuronal recordings, we here describe a system for simultaneous wide-field imaging of neuronal calcium activity from at least 20 Caenorhabditis elegans animals under precise microfluidic chemical stimulation. This increased experimental throughput was used to perform a systematic characterization of chemosensory neuron responses to multiple odors, odor concentrations, and temporal patterns, as well as responses to pharmacological manipulation. The system allowed recordings from sensory neurons and interneurons in freely moving animals, whose neuronal responses could be correlated with behavior. Wide-field imaging provides a tool for comprehensive circuit analysis with elevated throughput in C. elegans.
    No preview · Article · Oct 2013 · Proceedings of the National Academy of Sciences
  • Heeun Jang · Cornelia I Bargmann
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    ABSTRACT: The pheromone drop test is a simple and robust behavioral assay to quantify acute avoidance of pheromones in C. elegans, and the suppression of avoidance by attractive pheromones. In the pheromone drop test, water-soluble C. elegans pheromones are individually applied to animals that are freely moving on a large plate. Upon encountering a repellent, each C. elegans animal may or may not try to escape by making a long reversal. The fraction of animals that make a long reversal response indicates the repulsiveness of a given pheromone to a specific genotype/strain of C. elegans. Performing the drop test in the presence of bacterial food enhances the avoidance response to pheromones. Attraction to pheromones can be assayed by the suppression of reversals to repulsive pheromones or by the suppression of the basal reversal rate to buffer.
    No preview · Article · Sep 2013 · Methods in molecular biology (Clifton, N.J.)
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    ABSTRACT: Foraging animals have distinct exploration and exploitation behaviors that are organized into discrete behavioral states. Here, we characterize a neuromodulatory circuit that generates long-lasting roaming and dwelling states in Caenorhabditis elegans. We find that two opposing neuromodulators, serotonin and the neuropeptide pigment dispersing factor (PDF), each initiate and extend one behavioral state. Serotonin promotes dwelling states through the MOD-1 serotonin-gated chloride channel. The spontaneous activity of serotonergic neurons correlates with dwelling behavior, and optogenetic modulation of the critical MOD-1-expressing targets induces prolonged dwelling states. PDF promotes roaming states through a Gαs-coupled PDF receptor; optogenetic activation of cAMP production in PDF receptor-expressing cells induces prolonged roaming states. The neurons that produce and respond to each neuromodulator form a distributed circuit orthogonal to the classical wiring diagram, with several essential neurons that express each molecule. The slow temporal dynamics of this neuromodulatory circuit supplement fast motor circuits to organize long-lasting behavioral states.
    Preview · Article · Aug 2013 · Cell
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    Cornelia I Bargmann · Eve Marder
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    ABSTRACT: In this Historical Perspective, we ask what information is needed beyond connectivity diagrams to understand the function of nervous systems. Informed by invertebrate circuits whose connectivities are known, we highlight the importance of neuronal dynamics and neuromodulation, and the existence of parallel circuits. The vertebrate retina has these features in common with invertebrate circuits, suggesting that they are general across animals. Comparisons across these systems suggest approaches to study the functional organization of large circuits based on existing knowledge of small circuits.
    Full-text · Article · Jun 2013 · Nature Methods
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    ABSTRACT: Genetically encoded calcium indicators (GECIs) are powerful tools for systems neuroscience. Here we describe red, single-wavelength GECIs, "RCaMPs," engineered from circular permutation of the thermostable red fluorescent protein mRuby. High-resolution crystal structures of mRuby, the red sensor RCaMP, and the recently published red GECI R-GECO1 give insight into the chromophore environments of the Ca-bound state of the sensors and the engineered protein domain interfaces of the different indicators. We characterized the biophysical properties and performance of RCaMP sensors and in , larvae, and larval zebrafish. Further, we demonstrate 2-color calcium imaging both within the same cell (registering mitochondrial and somatic [Ca]) and between two populations of cells: neurons and astrocytes. Finally, we perform integrated optogenetics experiments, wherein neural activation channelrhodopsin-2 (ChR2) or a red-shifted variant, and activity imaging RCaMP or GCaMP, are conducted simultaneously, with the ChR2/RCaMP pair providing independently addressable spectral channels. Using this paradigm, we measure calcium responses of naturalistic and ChR2-evoked muscle contractions in crawling . We systematically compare the RCaMP sensors to R-GECO1, in terms of action potential-evoked fluorescence increases in neurons, photobleaching, and photoswitching. R-GECO1 displays higher Ca affinity and larger dynamic range than RCaMP, but exhibits significant photoactivation with blue and green light, suggesting that integrated channelrhodopsin-based optogenetics using R-GECO1 may be subject to artifact. Finally, we create and test blue, cyan, and yellow variants engineered from GCaMP by rational design. This engineered set of chromatic variants facilitates new experiments in functional imaging and optogenetics.
    Full-text · Article · Mar 2013 · Frontiers in Molecular Neuroscience
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    ABSTRACT: We describe an intensity-based glutamate-sensing fluorescent reporter (iGluSnFR) with signal-to-noise ratio and kinetics appropriate for in vivo imaging. We engineered iGluSnFR in vitro to maximize its fluorescence change, and we validated its utility for visualizing glutamate release by neurons and astrocytes in increasingly intact neurological systems. In hippocampal culture, iGluSnFR detected single field stimulus-evoked glutamate release events. In pyramidal neurons in acute brain slices, glutamate uncaging at single spines showed that iGluSnFR responds robustly and specifically to glutamate in situ, and responses correlate with voltage changes. In mouse retina, iGluSnFR-expressing neurons showed intact light-evoked excitatory currents, and the sensor revealed tonic glutamate signaling in response to light stimuli. In worms, glutamate signals preceded and predicted postsynaptic calcium transients. In zebrafish, iGluSnFR revealed spatial organization of direction-selective synaptic activity in the optic tectum. Finally, in mouse forelimb motor cortex, iGluSnFR expression in layer V pyramidal neurons revealed task-dependent single-spine activity during running.
    Full-text · Article · Jan 2013 · Nature Methods
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    ABSTRACT: Laser killing of cell nuclei has long been a powerful means of examining the roles of individual cells in 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 C. elegans.
    Full-text · Article · Dec 2012 · Methods in cell biology
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    Dataset: Figure S3
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    ABSTRACT: Genetic interactions between exp-1 and daf-7 in L4-stage animals. Bordering and aggregation behaviors of exp-1(ox276), daf-7(e1372), and double mutant L4-stage animals. Error bars, s.e.m. * P<0.05, ** P<0.01 by ANOVA with Dunnett test. ns, not significant. (TIF)
    Preview · Dataset · Dec 2012
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    Dataset: Figure S2
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    ABSTRACT: Genomic transgenes can rescue bordering and aggregation in exp-1 mutants. HW II-QTL NIL animals and exp-1(ox276) mutant animals were injected with N2-derived fosmids or plasmids depicted below. pAB05 is a genomic exp-1::GFP translational fusion that rescues the enteric defect of exp-1 but not aggregation and bordering; it is expressed in enteric muscles and in PDA, RID, ADE, and SABD neurons. Coinjection of clones (4) and (5), spanning 70 kb, rescued aggregation and bordering. At least three independent transgenic lines were tested for each injected DNA region, with consistent results. Error bars, s.e.m. * P<0.05, *** P<0.001 by ANOVA with Dunnett tests. ns, not significant. (TIF)
    Preview · Dataset · Dec 2012

Publication Stats

22k Citations
2,739.86 Total Impact Points


  • 2005-2015
    • The Rockefeller University
      • Lulu and Anthony Wang Laboratory of Neural Circuits and Behavior
      New York, New York, United States
  • 1991-2013
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States
  • 1992-2006
    • University of California, San Francisco
      • • Department of Biochemistry and Biophysics
      • • Department of Anatomy
      San Francisco, California, United States
  • 1998
    • University of Georgia
      • Department of Genetics
      Атина, Georgia, United States
    • Brandeis University
      • Department of Biology
      Волтам, Massachusetts, United States
  • 1997
    • Cold Spring Harbor Laboratory
      Cold Spring Harbor, New York, United States
    • California Institute of Technology
      • Division of Biology
      Pasadena, California, United States
  • 1990-1991
    • Massachusetts Institute of Technology
      • Department of Biology
      Cambridge, Massachusetts, United States
  • 1988
    • Whitehead Institute for Biomedical Research
      Cambridge, Massachusetts, United States