Arcuate hypothalamic AgRP and putative POMC neurons show opposite changes in spiking across multiple timescales
Open accessAbstract
Agouti-related-peptide (AgRP) neurons—interoceptive neurons in the arcuate nucleus of the hypothalamus (ARC)—are both necessary and sufficient for driving feeding behavior. To better understand the functional roles of AgRP neurons, we performed optetrode electrophysiological recordings from AgRP neurons in awake, behaving AgRP-IRES-Cre mice. In free-feeding mice, we observed a fivefold increase in AgRP neuron firing with mounting caloric deficit in afternoon vs morning recordings. In food-restricted mice, as food became available, AgRP neuron firing dropped, yet remained elevated as compared to firing in sated mice. The rapid drop in spiking activity of AgRP neurons at meal onset may reflect a termination of the drive to find food, while residual, persistent spiking may reflect a sustained drive to consume food. Moreover, nearby neurons inhibited by AgRP neuron photostimulation, likely including satiety-promoting pro-opiomelanocortin (POMC) neurons, demonstrated opposite changes in spiking. Finally, firing of ARC neurons was also rapidly modulated within seconds of individual licks for liquid food. These findings suggest novel roles for antagonistic AgRP and POMC neurons in the regulation of feeding behaviors across multiple timescales.
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AgRP activity is rapidly suppressed on sensory detection of food, suggesting that ongoing AgRP activity is dispensable for food consumption.
“However, AgRP activity is rapidly suppressed on sensory detection of food227,228,230, which, surprisingly, suggests that ongoing AgRP activity is dispensable for food consumption.”
From Neural mechanisms of social homeostasis (2019) · cites this paper as [228]
AgRP neurons are activated in energy deficit, and their optical stimulation promotes food consumption but also elicits real-time place avoidance in the absence of food.
“AgRP neurons are activated in a state of energy deficit228, and their optical stimulation can voraciously promote food consumption, but also elicits real-time place avoidance (indicative of an aversive state) in the absence of food173,227,229.”
From Neural mechanisms of social homeostasis (2019) · cites this paper as [228]
AgRP neurons are inhibited by overfeeding and satiety signals.
“and inhibited by overfeeding and satiety signals [23–25].”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [23]
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References 72 · Cited by 290
- Authors
- Mandelblat-Cerf, Y., Ramesh, R. N., Burgess, C. R., Patella, P., Yang, Z., Lowell, B. B., & Andermann, M. L.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Andermann, Mark L
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2015-07-10
- Volume
- 4
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC4498165
- OpenAlex
- W1940814527
- Cited by
- 290
- References
- 72
- Citations by year
- 2026: 15 · 2025: 39 · 2024: 27 · 2023: 23 · 2022: 28 · 2021: 29 · 2020: 25 · 2019: 37 · 2018: 24 · 2017: 24 · 2016: 17 · 2015: 2
- FWCI
- 12.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Davis Family Foundation (Postdoctoral Fellowship Program in Eating Disorders Research)
- National Institutes of Health (NIH) (Director's New Innovator Award, DP2DK105570-01, R01 DK089044, P30 DK057521, P30 DK046200, R01 DK096010)
- Klarman Family Foundation (Grants Program in Eating Disorders Research)
- Richard and Susan Smith Family Foundation (Awards Program for Excellence in Biomedical Research)
- Pew Charitable Trusts (Pew Scholars Program in the Biomedical Sciences)
- 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, POMC neurons, arcuate nucleus, hypothalamus, feeding behavior, neuronal firing, dietary restriction, satiety, photostimulation, caloric deficit
- MeSH terms
- Action Potentials, Animals, Arcuate Nucleus of Hypothalamus, Feeding Behavior, Neurons, Pro-Opiomelanocortin, Mice, Agouti-Related Protein
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