Ucn3 and CRF-R2 in the medial amygdala regulate complex social dynamics

Yair Shemesh, Oren Forkosh, Mathias Mahn, Sergey Anpilov, Yehezkel Sztainberg, Sharon Manashirov, Tamar Shlapobersky, Evan Elliott, Laure Tabouy, Gili Ezra, Elaine S. Adler, Yair J. Ben-Efraim, Shosh Gil, Yael Kuperman, Sharon Haramati, Julien Dine, Matthias Eder, Jan M. Deussing, Elad Schneidman, Ofer YizharAlon Chen

Research output: Contribution to journalArticlepeer-review

73 Scopus citations


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.

Original languageEnglish
Pages (from-to)1489-1496
Number of pages8
JournalNature Neuroscience
Issue number11
StatePublished - Nov 2016

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