Hunger neurons drive feeding through a sustained, positive reinforcement signal
- University of California, 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.
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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).
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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Hunger neurons drive feeding through a sustained, positive reinforcement signal
eLife 5:e18640.
https://doi.org/10.7554/eLife.18640
