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Raphe GABAergic Neurons Mediate the Acquisition of Avoidance after Social Defeat
Open accessAbstract
Serotonin (5-HT) modulates neural responses to socioaffective cues and can bias approach or avoidance behavioral decisions, yet the cellular mechanisms underlying its contribution to the regulation of social experiences remain poorly understood. We hypothesized that GABAergic neurons in the dorsal raphe nucleus (DRN) may participate in socioaffective regulation by controlling serotonergic tone during social interaction. We tested this hypothesis using whole-cell recording techniques in genetically identified DRN GABA and 5-HT neurons in mice exposed to social defeat, a model that induces long-lasting avoidance behaviors in a subset of mice responsive to serotonergic antidepressants. Our results revealed that social defeat engaged DRN GABA neurons and drove GABAergic sensitization that strengthened inhibition of 5-HT neurons in mice that were susceptible, but not resilient to social defeat. Furthermore, optogenetic silencing of DRN GABA neurons disinhibited neighboring 5-HT neurons and prevented the acquisition of social avoidance in mice exposed to a social threat, but did not affect a previously acquired avoidance phenotype. We provide the first characterization of GABA neurons in the DRN that monosynaptically inhibit 5-HT neurons and reveal their key role in neuroplastic processes underlying the development of social avoidance.
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“Yet, this increased reliance on the spectator relative to the actor model following uncontrollable stressors probably involves several other brain areas, including the mPFC and the dorsal raphe nucleus, both of which are highly sensitive to stressor controllability [14][15][16] .”
From Stress-sensitive inference of task controllability (2022) · cites this paper as [16]
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Si, T., Han, H., Zhang, Y., Zhou, Z., Li, Z., Cao, J., & Zang, W. D. (2026) · iScience · doi:10.1016/j.isci.2026.117569
Cellular and molecular coding of habit-driven behavior in the dorsal raphe nucleusPreprint
Chalençon, L., Rahn, R., Chottekalapanda, R. U., Lenz, A., Zhang, T., Donatelle, A., Stujenske, J. M., Fetcho, R. N., Parekh, P. K., Roshgadol, J., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.01.755903
Metadata
- Authors
- Challis, C., Boulden, J., Veerakumar, A., Espallergues, J., Vassoler, F. M., Pierce, R. C., Beck, S. G., & Berton, O.
- Affiliations
- University of Pennsylvania (US)
- Children's Hospital of Philadelphia (US)
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-08-28
- Volume
- 33
- Issue
- 35
- Pages
- 13978-13988
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3756748
- OpenAlex
- W2010788510
- Cited by
- 197
- References
- 68
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 16 · 2023: 10 · 2022: 14 · 2021: 14 · 2020: 18 · 2019: 15 · 2018: 17 · 2017: 21 · 2016: 10 · 2015: 20 · 2014: 25 · 2013: 2
- FWCI
- 9.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- International Mental Health Research Organization
- National Institutes of Health (DA22339, DA18678)
- National Institute of Mental Health (R01MH087581, MH0754047, F31MH097386, RC1MH089800, T32MH014654, MH087581, MH089800)
- National Institute on Drug Abuse (DA22339, DA18678, R01DA022339, K02DA018678)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- dorsal raphe nucleus, GABAergic neurons, serotonergic neurons, social defeat, social avoidance, social resilience, optogenetic silencing, neuroplasticity, social interaction
- MeSH terms
- Aggression, Animals, Avoidance Learning, Male, Mice, Inbred C57BL, Phenotype, Raphe Nuclei, Excitatory Postsynaptic Potentials, Mice, Inhibitory Postsynaptic Potentials, Serotonergic Neurons, GABAergic Neurons, Optogenetics
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