title: Ucn3 and CRF-R2 in the medial amygdala regulate complex social dynamics.
abstract: Social encounters are associated with varying degrees of emotional arousal and stress. The mechanisms underlying adequate socioemotional balance are unknown. The medial amygdala (MeA) is a brain region associated with social behavior in mice. Corticotropin-releasing factor receptor type-2 (CRF-R2) and its specific ligand urocortin-3 (Ucn3), known components of the behavioral stress response system, are highly expressed in the MeA. Here we show that mice deficient in CRF-R2 or Ucn3 exhibit abnormally low preference for novel conspecifics. MeA-specific knockdown of Crfr2 (Crhr2) in adulthood recapitulated this phenotype. In contrast, pharmacological activation of MeA CRF-R2 or optogenetic activation of MeA Ucn3 neurons increased preference for novel mice. Furthermore, chemogenetic inhibition of MeA Ucn3 neurons elicited pro-social behavior in freely behaving groups of mice without affecting their hierarchal structure. These findings collectively suggest that the MeA Ucn3-CRF-R2 system modulates the ability of mice to cope with social challenges.
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.|Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Yair
authors.initials: Y
authors.lastname: Shemesh
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.|Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Oren
authors.initials: O
authors.lastname: Forkosh
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Mathias
authors.initials: M
authors.lastname: Mahn
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.|Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Sergey
authors.initials: S
authors.lastname: Anpilov
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yehezkel
authors.initials: Y
authors.lastname: Sztainberg
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.|Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Sharon
authors.initials: S
authors.lastname: Manashirov
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.|Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Tamar
authors.initials: T
authors.lastname: Shlapobersky
authors.affiliation: Faculty of Medicine, Bar Ilan University, Safed, Israel.
authors.forename: Evan
authors.initials: E
authors.lastname: Elliott
authors.affiliation: Faculty of Medicine, Bar Ilan University, Safed, Israel.
authors.forename: Laure
authors.initials: L
authors.lastname: Tabouy
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.|Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Gili
authors.initials: G
authors.lastname: Ezra
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.|Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Adler
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.|Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Yair J
authors.initials: YJ
authors.lastname: Ben-Efraim
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.|Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Shosh
authors.initials: S
authors.lastname: Gil
authors.affiliation: Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Kuperman
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Sharon
authors.initials: S
authors.lastname: Haramati
authors.affiliation: Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Julien
authors.initials: J
authors.lastname: Dine
authors.affiliation: Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Eder
authors.affiliation: Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Deussing
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Elad
authors.initials: E
authors.lastname: Schneidman
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ofer
authors.identifier: 0000-0003-4228-1448
authors.initials: O
authors.lastname: Yizhar
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.|Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Alon
authors.initials: A
authors.lastname: Chen
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D007266:Inhibition, Psychological; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D012919:Social Behavior; D054832:Urocortins / Q000235:genetics / Q000378:metabolism*
chemical_list: C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone; C000602668:Ucn3 protein, mouse; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone