title: Raphe GABAergic neurons mediate the acquisition of avoidance after social defeat.
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.
authors.affiliation: Department of Psychiatry and Neuroscience Graduate Group, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Collin
authors.initials: C
authors.lastname: Challis
authors.forename: Janette
authors.initials: J
authors.lastname: Boulden
authors.forename: Avin
authors.initials: A
authors.lastname: Veerakumar
authors.forename: Julie
authors.initials: J
authors.lastname: Espallergues
authors.forename: Fair M
authors.initials: FM
authors.lastname: Vassoler
authors.forename: R Christopher
authors.initials: RC
authors.lastname: Pierce
authors.forename: Sheryl G
authors.initials: SG
authors.lastname: Beck
authors.forename: Olivier
authors.initials: O
authors.lastname: Berton
mesh_terms: D000374:Aggression; D000818:Animals; D001362:Avoidance Learning; D019706:Excitatory Postsynaptic Potentials; D059330:GABAergic Neurons / Q000502:physiology*; D053444:Inhibitory Postsynaptic Potentials; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D062308:Optogenetics; D010641:Phenotype; D011903:Raphe Nuclei / Q000166:cytology* / Q000502:physiology; D059326:Serotonergic Neurons / Q000502:physiology*