Dendritic remodeling of D1 neurons by RhoA/Rho-kinase mediates depression-like behavior.

ABSTRACT: Depression alters the structure and function of brain reward circuitry. Preclinical evidence suggests that medium spiny neurons (MSNs) in the nucleus accumbens (NAc) undergo structural plasticity; however, the molecular mechanism and behavioral significance is poorly understood. Here we report that atrophy of D1, but not D2 receptor containing MSNs is strongly associated with social avoidance in mice subject to social defeat stress. D1-MSN atrophy is caused by cell-type specific upregulation of the GTPase RhoA and its effector Rho-kinase. Pharmacologic and genetic reduction of activated RhoA prevents depressive outcomes to stress by preventing loss of D1-MSN dendritic arbor. Pharmacologic and genetic promotion of activated RhoA enhances depressive outcomes by reducing D1-MSN dendritic arbo

SUBMITTER: Fox ME 

PROVIDER: S-EPMC6378138 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature