Hunger neurons drive feeding through a sustained, positive reinforcement signal.
Open accessAbstract
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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Brief optical stimulation, as little as 1 min, prior to food availability was sufficient to promote robust, sustained feeding in well-fed mice once food was made available.
“This paradox is potentially reconciled by the observation that brief optical stimulation, as little as 1 min, prior to food availability was sufficient to promote robust, sustained feeding in well-fed mice once food was made available231.”
From Neural mechanisms of social homeostasis (2019) · cites this paper as [231]
Prestimulation was insufficient to drive drinking behavior when water was subsequently made available for SFO NOS1 neurons.
“Intriguingly, this is not a feature of SFO NOS1 neurons, as prestimulation was insufficient to drive drinking behavior when water was subsequently made available231.”
From Neural mechanisms of social homeostasis (2019) · cites this paper as [231]
Mice will actually work to turn on their hypothalamic AgRP neurons that previously made them eat, indicating that the increased appetite can be dissociated from negative valence, and even take on a positive valence in the right conditions.
“However, other neuroscientists have found that mice will actually work to turn on their hypothalamic AgRP neurons that previously made them eat, indicating that the increased appetite can be dissociated from negative valence, and even take on a positive valence in the right conditions (Chen et al., 2016).”
From Evolving Concepts of Emotion and Motivation (2018) · cites this paper as Chen et al., 2016
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- Authors
- Chen, Y., Lin, Y.-C., Zimmerman, C. A., Essner, R. A., & Knight, Z. A.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Knight, Zachary A
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2016-08-24
- Volume
- 5
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC5016090
- OpenAlex
- W2513909731
- Cited by
- 196
- References
- 61
- Citations by year
- 2026: 12 · 2025: 22 · 2024: 16 · 2023: 20 · 2022: 20 · 2021: 26 · 2020: 26 · 2019: 19 · 2018: 19 · 2017: 12 · 2016: 4
- FWCI
- 11.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK106399, P30DK098722, P30DK063720, DP2DK019342)
- National Institute of Neurological Disorders and Stroke (R01NS094781)
- New York Stem Cell Foundation (Robertson Investigator Award)
- American Diabetes Association (Pathway Accelerator Award)
- Rita Allen Foundation (Rita Allen Scholar)
- Alfred P. Sloan Foundation
- McKnight Endowment Fund for Neuroscience
- Brain and Behavior Research Foundation
- UCSF Program for Breakthrough Biological Research
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- AgRP neurons, feeding behavior, positive reinforcement, food reward, negative energy balance, optogenetic stimulation, appetitive behavior, consummatory behavior, behavioral state transitions
- MeSH terms
- Action Potentials, Animals, Feeding Behavior, Hunger, Neurons, Mice, Agouti-Related Protein, Optogenetics
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