Hunger neurons drive feeding through a sustained, positive reinforcement signal

Author:

Chen Yiming123,Lin Yen-Chu12,Zimmerman Christopher A123,Essner Rachel A12,Knight Zachary A123ORCID

Affiliation:

1. Department of Physiology, University of California, San Francisco, San Francisco, United States

2. Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, United States

3. Neuroscience Graduate Program, University of California, San Francisco, San Francisco, United states

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.

Funder

National Institute of Diabetes and Digestive and Kidney Diseases

National Institute of Neurological Disorders and Stroke

New York Stem Cell Foundation

American Diabetes Association

Rita Allen Foundation

Alfred P. Sloan Foundation

McKnight Endowment Fund for Neuroscience

Brain and Behavior Research Foundation

UCSF Program for Breakthrough Biological Research

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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