Cited by 1,157Regulation of Appetite and ObesityHypothalamic control of reproductive hormonesNeurotransmitter Receptor Influence on Behavior

AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training

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Aponte, Yexica, Atasoy, Deniz, Sternson, Scott M·2011·Nature Neuroscience

Abstract

Two intermingled hypothalamic neuron populations specified by expression of agouti-related peptide (AGRP) or pro-opiomelanocortin (POMC) positively and negatively influence feeding behavior, respectively, possibly by reciprocally regulating downstream melanocortin receptors. However, the sufficiency of these neurons to control behavior and the relationship of their activity to the magnitude and dynamics of feeding are unknown. To measure this, we used channelrhodopsin-2 for cell type-specific photostimulation. Activation of only 800 AGRP neurons in mice evoked voracious feeding within minutes. The behavioral response increased with photoexcitable neuron number, photostimulation frequency and stimulus duration. Conversely, POMC neuron stimulation reduced food intake and body weight, which required melanocortin receptor signaling. However, AGRP neuron-mediated feeding was not dependent on suppressing this melanocortin pathway, indicating that AGRP neurons directly engage feeding circuits. Furthermore, feeding was evoked selectively over drinking without training or prior photostimulus exposure, which suggests that AGRP neurons serve a dedicated role coordinating this complex behavior.

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Authors
Aponte, Y., Atasoy, D., & Sternson, S. M.
Affiliations
Howard Hughes Medical Institute (US)
Corresponding author
Sternson, Scott M
Venue
Nature Neuroscience
Published
2011-01-05
Volume
14
Issue
3
Pages
351-355
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W2139359479
Cited by
1,157
References
38
Citations by year
2026: 40 · 2025: 91 · 2024: 82 · 2023: 79 · 2022: 79 · 2021: 94 · 2020: 78 · 2019: 74 · 2018: 90 · 2017: 93 · 2016: 88 · 2015: 82 · 2014: 59 · 2013: 55 · 2012: 45
FWCI
27.63
Type
journal article
Language
en
Open access
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
Howard Hughes Medical Institute
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
AgRP neurons, feeding behavior, hypothalamus, proopiomelanocortin neurons, melanocortin receptors, optogenetic stimulation, channelrhodopsin-2, dietary intake, body weight, anorexigenic neurons
MeSH terms
Channelrhodopsins, Animals, Behavior, Animal, Conditioning, Classical, Eating, Feeding Behavior, Hypothalamus, Neurons, Photic Stimulation, Pro-Opiomelanocortin, Recombinant Fusion Proteins, Mice, Melanocortins, Agouti-Related Protein

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