Navin Pokala

New York Institute of Technology

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Cornelia I. Bargmann

Rockefeller University

Steven W. Flavell

Massachusetts Institute of Technology

Tracy M. Handel

University of Montana

Sharon C. Goldsmith

Albert Einstein College of Medicine

Evan Z. Macosko

Broad Institute

Steven C. Almo

Albert Einstein College of Medicine

Eduardo J. Izquierdo

Indiana University Bloomington

Patrick T. McGrath

Georgia Institute of Technology

Qiang Liu

City University of Hong Kong

Randy F. Stout

New York Institute of Technology

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Howard Hughes Medical Institute

Rockefeller University

University of California, Berkeley

Harvard University

University of California, San Francisco

University of California, San Diego

California Institute of Technology

University of Oregon

Massachusetts Institute of Technology

Salk Institute for Biological Studies

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Oxytocin/Vasopressin-Related Peptides Have an Ancient Role in Reproductive Behavior

Science (2012)

Jennifer L. Garrison Evan Z. Macosko Samantha Bernstein Navin Pokala Dirk R. Albrecht

Many biological functions are conserved, but the extent to which conservation applies to integrative behaviors is unknown. Vasopressin and oxytocin neuropeptides are strongly implicated in mammalian reproductive and social behaviors, yet rodent loss-of-function mutants have relatively subtle behavioral defects. Here we identify an oxytocin/vasopressin-like signaling system in Caenorhabditis elegans, consisting of a peptide and two receptors that are expressed in sexually dimorphic patterns. Males lacking the peptide or its receptors perform poorly in reproductive behaviors, including mate search, mate recognition, and mating, but other sensorimotor behaviors are intact. Quantitative analysis indicates that mating motor patterns are fragmented and inefficient in mutants, suggesting that oxytocin/vasopressin peptides increase the coherence of mating behaviors. These results indicate that conserved molecules coordinate diverse behavioral motifs in reproductive behavior.

Oxytocin receptor

Reproductive behavior

10.1126/science.1226201

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Citations (250)

A hub-and-spoke circuit drives pheromone attraction and social behaviour in C. elegans

Nature (2009)

Evan Z. Macosko Navin Pokala Evan H. Feinberg Sreekanth H. Chalasani Rebecca A. Butcher

Sensory neuron

Hermaphrodite

10.1038/nature07886

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Citations (484)

Parallel multimodal circuits control an innate foraging behavior

bioRxiv (Cold Spring Harbor Laboratory) (2018)

Alejandro López-Cruz Navin Pokala Aylesse Sordillo Steven W. Flavell Patrick T. McGrath

SUMMARY Foraging strategies that enable animals to locate food efficiently are composed of highly conserved behavioral states with characteristic features. Here, we identify parallel multimodal circuit modules that control an innate foraging state -- local search behavior -- after food removal in the nematode Caenorhabditis elegans . Two parallel groups of chemosensory and mechanosensory glutamatergic neurons that detect food-related cues trigger local search by inhibiting separate integrating neurons through a metabotropic glutamate receptor, MGL-1. The chemosensory and mechanosensory modules are separate and redundant, as glutamate release from either can drive the full behavior. Spontaneous activity in the chemosensory module encodes information about the time since the last food encounter and correlates with the foraging behavior. In addition, the ability of the sensory modules to control local search is gated by the internal nutritional state of the animal. This multimodal circuit configuration provides robust control of an innate adaptive behavior.

10.1101/326405

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Histamine-HisCl1 system for C elegans v1

Navin Pokala Cornelia I. Bargmann

We describe a chemical-genetic approach for inducible silencing ofCaenorhabditis elegansneurons in intact animals, using the histamine-gated chloride channel HisCl1 fromDrosophilaand exogenous histamine. Administering histamine to freely movingC. elegansthat express HisCl1 transgenes in neurons leads to rapid and potent inhibition of neural activity within minutes.C. elegansdoes not use histamine as an endogenous neurotransmitter, and exogenous histamine has little apparent effect on wild-typeC. elegansbehavior.

Biogenic amine

Histamine N-methyltransferase

10.17504/protocols.io.mumc6u6

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Serotonin and the Neuropeptide PDF Initiate and Extend Opposing Behavioral States in C. elegans

Cell (2013)

Steven W. Flavell Navin Pokala Evan Z. Macosko Dirk R. Albrecht Johannes Larsch

10.1016/j.cell.2013.08.001

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Citations (426)

Inducible and titratable silencing ofCaenorhabditis elegansneurons in vivo with histamine-gated chloride channels

Proceedings of the National Academy of Sciences (2014)

Navin Pokala Qiang Liu Andrew Gordus Cornelia I. Bargmann

Significance Inducible silencing of neurons is a powerful method for studying the functions of neural circuits. We describe a system for inducible silencing of Caenorhabditis elegans neurons, based on transgenic C. elegans nematodes engineered to produce the inhibitory Drosophila histamine-gated chloride channel (HisCl1) in specific neurons. The activity of HisCl1-expressing neurons is acutely and reversibly silenced by exogenous histamine, which C. elegans absorbs from the media. In addition to completely silencing neurons, the histamine-HisCl1 system can be used to titrate neural activity, demonstrating quantitative relationships between neural activity and behavior. The histamine-HisCl1 system is complementary to other methods of monitoring and manipulating neuronal activity, providing opportunities for combinatorial control of circuits.

Biological neural network

Chloride channel

10.1073/pnas.1400615111

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Citations (219)

Energy Functions for Protein Design: Adjustment with Protein–Protein Complex Affinities, Models for the Unfolded State, and Negative Design of Solubility and Specificity

Journal of Molecular Biology (2005)

Navin Pokala Tracy M. Handel

Protein design

Conformational isomerism

Accessible surface area

10.1016/j.jmb.2004.12.019