|Title||Cell-type-specific role for nucleus accumbens neuroligin-2 in depression and stress susceptibility.|
|Publication Type||Journal Article|
|Year of Publication||2018|
|Auteurs||Heshmati, M, Aleyasin, H, Menard, C, Christoffel, DJ, Flanigan, ME, Pfau, ML, Hodes, GE, Lepack, AE, Bicks, LK, Takahashi, A, Chandra, R, Turecki, G, Lobo, MKay, Maze, I, Golden, SA, Russo, SJ|
|Journal||Proc Natl Acad Sci U S A|
|Date Published||2018 Jan 30|
Behavioral coping strategies are critical for active resilience to stress and depression; here we describe a role for neuroligin-2 (NLGN-2) in the nucleus accumbens (NAc). Neuroligins (NLGN) are a family of neuronal postsynaptic cell adhesion proteins that are constituents of the excitatory and inhibitory synapse. Importantly, NLGN-3 and NLGN-4 mutations are strongly implicated as candidates underlying the development of neuropsychiatric disorders with social disturbances such as autism, but the role of NLGN-2 in neuropsychiatric disease states is unclear. Here we show a reduction in NLGN-2 gene expression in the NAc of patients with major depressive disorder. Chronic social defeat stress in mice also decreases NLGN-2 selectively in dopamine D1-positive cells, but not dopamine D2-positive cells, within the NAc of stress-susceptible mice. Functional NLGN-2 knockdown produces bidirectional, cell-type-specific effects: knockdown in dopamine D1-positive cells promotes subordination and stress susceptibility, whereas knockdown in dopamine D2-positive cells mediates active defensive behavior. These findings establish a behavioral role for NAc NLGN-2 in stress and depression; provide a basis for targeted, cell-type specific therapy; and highlight the role of active behavioral coping mechanisms in stress susceptibility.