1. Neuroscience
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Hunger neurons drive feeding through a sustained, positive reinforcement signal

  1. Yiming Chen
  2. Yen-Chu Lin
  3. Christopher Zimmerman
  4. Rachel A Essner
  5. Zachary A Knight  Is a corresponding author
  1. University of California, San Francisco, United States
Research Article
  • Cited 87
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Cite this article as: eLife 2016;5:e18640 doi: 10.7554/eLife.18640

Abstract

The neural mechanisms underlying hunger are poorly understood. AgRP neurons are activated by energy deficit and promote voracious food consumption, suggesting these cells may supply the fundamental hunger drive that motivates feeding. However recent in vivo recording experiments revealed that AgRP neurons are inhibited within seconds by the sensory detection of food, raising the question of how these cells can promote feeding at all. Here we resolve this paradox by showing that brief optogenetic stimulation of AgRP neurons before food availability promotes intense appetitive and consummatory behaviors that persist for tens of minutes in the absence of continued AgRP neuron activation. We show that these sustained behavioral responses are mediated by a long-lasting potentiation of the rewarding properties of food and that AgRP neuron activity is positively reinforcing. These findings reveal that hunger neurons drive feeding by transmitting a positive valence signal that triggers a stable transition between behavioral states.

Article and author information

Author details

  1. Yiming Chen

    Department of Physiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Yen-Chu Lin

    Department of Physiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Christopher Zimmerman

    Department of Physiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Rachel A Essner

    Department of Physiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Zachary A Knight

    Department of Physiology, University of California, San Francisco, San Francisco, United States
    For correspondence
    zachary.knight@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7621-1478

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK106399)

  • Zachary A Knight

Brain and Behavior Research Foundation

  • Zachary A Knight

National Institute of Neurological Disorders and Stroke (R01NS094781)

  • Zachary A Knight

New York Stem Cell Foundation (Robertson Investigator Award)

  • Zachary A Knight

American Diabetes Association (Pathway Accelerator Award)

  • Zachary A Knight

Rita Allen Foundation (Rita Allen Scholar)

  • Zachary A Knight

Alfred P. Sloan Foundation

  • Zachary A Knight

McKnight Endowment Fund for Neuroscience

  • Zachary A Knight

National Institute of Diabetes and Digestive and Kidney Diseases (P30DK098722)

  • Zachary A Knight

National Institute of Diabetes and Digestive and Kidney Diseases (P30DK063720)

  • Zachary A Knight

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All experiments were approved by the UCSF institutional animal care and use committee (IACUC protocol AN133011).

Reviewing Editor

  1. Joseph S Takahashi, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, United States

Publication history

  1. Received: June 9, 2016
  2. Accepted: August 23, 2016
  3. Accepted Manuscript published: August 24, 2016 (version 1)
  4. Version of Record published: September 8, 2016 (version 2)

Copyright

© 2016, Chen et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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Further reading

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