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.
| Original language | English |
|---|---|
| Pages (from-to) | 1489-1496 |
| Number of pages | 8 |
| Journal | Nature Neuroscience |
| Volume | 19 |
| Issue number | 11 |
| Early online date | 18 Jul 2016 |
| DOIs | |
| Publication status | Published - Nov 2016 |
Funding
We thank S. Ovadia for his devoted assistance with animal care. We thank J. Keverne for professional English editing, formatting and scientific input. This work is supported by an FP7 grant from the European Research Council (260463; A.C.); research grants from the Israel Science Foundation (1565/15) (A.C.); research support from Roberto and Renata Ruhman (A.C.); research support from Bruno and Simone Licht; I-CORE Program of the Planning and Budgeting Committee and The Israel Science Foundation (grant no. 1916/12 to A.C.); the Nella and Leon Benoziyo Center for Neurological Diseases (A.C.); the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics (A.C.); the Perlman Family Foundation, founded by Louis L. and Anita M. Perlman (A.C.); the Adelis Foundation (A.C.); the Irving I. Moskowitz Foundation (A.C.); grants from the Israel Science Foundation (1351/12) and the European Commission (ERC StG #337637 and Marie Curie CIG #321919) (O.Y.) and a Human Frontier Program career development award (O.Y.); a Human Frontier Science Program grant (E.S.); European Research Council grant # 311238 (E.S.); an Israel Science Foundation grant #1629/12 (E.S.); research support from Martin Kushner Schnur (E.S.); and Mr. and Mrs. Lawrence Feis (E.S.). Contributions - Y. Shemesh and O.F. designed and performed most of the experiments. M.M., M.E., J.D., and J.M.D. designed and performed electrophysiological studies. S.A., S.M., T.S., E.E., L.T., G.E., E.S.A., Y.J.B.-E., S.G., Y.K., and S.H. assisted in experiments. Y. Shemesh, Y. Sztainberg, and O.F. wrote the code for analyzing behavior and validated it. E.S., O.Y., and A.C. conceived, designed, and supervised the project. Y. Shemesh, O.F., and A.C. wrote the manuscript.
All Science Journal Classification (ASJC) codes
- General Neuroscience