Sustained NPY signaling enables AgRP neurons to drive feeding
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
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.
Reviewing Editor
- Richard D Palmiter, Howard Hughes Medical Institute, University of Washington, United States
Publication history
- Received: February 26, 2019
- Accepted: April 26, 2019
- Accepted Manuscript published: April 29, 2019 (version 1)
- Version of Record published: May 13, 2019 (version 2)
Copyright
© 2019, 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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