Cited by 197Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchTreatment of Major Depression

Raphe GABAergic Neurons Mediate the Acquisition of Avoidance after Social Defeat

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Challis, C., Boulden, J., Veerakumar, A., Espallergues, J., Vassoler, F. M., Pierce, R. C., Beck, S. G., Berton, O.·2013·Journal of Neuroscience

Abstract

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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  • Following uncontrollable stressors, increased reliance on the spectator relative to the actor model probably involves several other brain areas, including the mPFC and the dorsal raphe nucleus.

    “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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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
Published
2013-08-28
Volume
33
Issue
35
Pages
13978-13988
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
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
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 › 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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