Publication Type:
Journal ArticleSource:
Proc Natl Acad Sci U S A, Volume 115, Issue 5, p.1111-1116 (2018)Keywords:
Aggression, Animals, Antidepressive Agents, Behavior, Animal, Cell Adhesion Molecules, Neuronal, Cell Line, Depressive Disorder, Major, Disease Models, Animal, Dominance-Subordination, Heterozygote, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, MicroRNAs, Nerve Tissue Proteins, Nucleus Accumbens, Receptors, Dopamine D1, Receptors, Dopamine D2, RNA, Messenger, Social Behavior, Stress, Psychological, SynapsesAbstract:
<p>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.</p>
