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Role of BDNF in the development of an OFC-amygdala circuit regulating sociability in mouse and human.

TitleRole of BDNF in the development of an OFC-amygdala circuit regulating sociability in mouse and human.
Publication TypeJournal Article
Year of Publication2019
AuthorsLi A, Jing D, Dellarco DV, Hall BS, Yang R, Heilberg RT, Huang C, Liston C, Casey BJ, Lee FS
JournalMol Psychiatry
Date Published2019 Apr 16
ISSN1476-5578
Abstract

Social deficits are common in many psychiatric disorders. However, due to inadequate tools for manipulating circuit activity in humans and unspecific paradigms for modeling social behaviors in rodents, our understanding of the molecular and circuit mechanisms mediating social behaviors remains relatively limited. Using human functional neuroimaging and rodent fiber photometry, we identified a mOFC-BLA projection that modulates social approach behavior and influences susceptibility to social anxiety. In humans and knock-in mice with a loss of function BDNF SNP (Val66Met), the functionality of this circuit was altered, resulting in social behavioral changes in human and mice. We further showed that the development of this circuit is disrupted in BDNF Met carriers due to insufficient BDNF bioavailability, specifically during a peri-adolescent timeframe. These findings define one mechanism by which social anxiety may stem from altered maturation of orbitofronto-amygdala projections and identify a developmental window in which BDNF-based interventions may have therapeutic potential.

DOI10.1038/s41380-019-0422-4
Alternate JournalMol. Psychiatry
PubMed ID30992540
Grant ListNS052819 / / Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) /
5UL1TR000457 / / Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) /
GM07739 / / Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) /
P50MH079513 / / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) /
R01DA018879 / / U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) /
RC2DA029475 / / U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) /