Cell-type-specific role for nucleus accumbens neuroligin-2 in depression and stress susceptibility.
Title | Cell-type-specific role for nucleus accumbens neuroligin-2 in depression and stress susceptibility. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Heshmati M, Aleyasin H, Ménard 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 |
Volume | 115 |
Issue | 5 |
Pagination | 1111-1116 |
Date Published | 2018 Jan 30 |
ISSN | 1091-6490 |
Abstract | 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. |
DOI | 10.1073/pnas.1719014115 |
Alternate Journal | Proc. Natl. Acad. Sci. U.S.A. |
PubMed ID | 29339486 |
PubMed Central ID | PMC5798379 |
Grant List | FI2 GM117583 / GM / NIGMS NIH HHS / United States F31 MH105217 / MH / NIMH NIH HHS / United States F30 MH100835 / MH / NIMH NIH HHS / United States T32 MH087004 / MH / NIMH NIH HHS / United States P50 MH096890 / MH / NIMH NIH HHS / United States R01 MH114882 / MH / NIMH NIH HHS / United States R01 MH090264 / MH / NIMH NIH HHS / United States P50 AT008661 / AT / NCCIH NIH HHS / United States T32 MH096678 / MH / NIMH NIH HHS / United States |