Sustained NPY signaling enables AgRP neurons to drive feeding

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Abstract

Artificial stimulation of Agouti-Related Peptide (AgRP) neurons promotes intense food consumption, yet paradoxically during natural behavior these cells are inhibited before feeding begins. To reconcile these observations, we showed in a previous paper (Chen et al., 2016) that brief stimulation of AgRP neurons can generate hunger that persists for tens of minutes, but the mechanisms underlying this sustained hunger drive remain unknown. Here we show that Neuropeptide Y (NPY) is uniquely required for the long-lasting effects of AgRP neurons on feeding behavior. We blocked the ability of AgRP neurons to signal through AgRP, NPY, or GABA, and then stimulated these cells using a paradigm that mimics their natural regulation. Deletion of NPY, but not AgRP or GABA, abolished optically-stimulated feeding, and this was rescued by NPY re-expression selectively in AgRP neurons. These findings reveal a unique role for NPY in sustaining hunger in the interval between food discovery and consumption.

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All data generated or analysed during this study are included in the manuscript and supporting files.

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Yiming Chen

Neuroscience Graduate Program, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
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.
Seher Kosar

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

Competing interests
The authors declare that no competing interests exist.
Oliver H Miller

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

Competing interests
The authors declare that no competing interests exist.
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.
Sheyda Mesgarzadeh

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

Competing interests
The authors declare that no competing interests exist.
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.

"This ORCID iD identifies the author of this article:" 0000-0001-7621-1478

Funding

National Institutes of Health (R01DK106399)

Zachary A Knight

National Institutes of Health (R01NS094781)

Zachary A Knight

Howard Hughes Medical Institute

Zachary A Knight

American Diabetes Association (ADA Accelerator Grant)

Zachary A Knight

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

Copyright

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.