Impaired microglia-mediated synaptic pruning in the nucleus accumbens during adolescence results in persistent dysregulation of familiar, but not novel social interactions in sex-specific ways

青春期伏隔核中小胶质细胞介导的突触修剪受损,导致性别特异性的熟悉社交互动持续失调,但不会出现新的社交互动

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作者:Julia M Kirkland, Erin L Edgar, Ishan Patel, Ashley M Kopec

Abstract

Evolutionarily conserved, peer-directed social behaviors are essential to participate in many aspects of human society. These behaviors directly impact psychological, physiological, and behavioral maturation. Adolescence is an evolutionarily conserved period during which reward-related behaviors, including social behaviors, develop via developmental plasticity in the mesolimbic dopaminergic 'reward' circuitry of the brain. The nucleus accumbens (NAc) is an intermediate reward relay center that develops during adolescence and mediates both social behaviors and dopaminergic signaling. In several developing brain regions, synaptic pruning mediated by microglia, the resident immune cells of the brain, is important for normal behavioral development. In rats, we previously demonstrated that microglial synaptic pruning also mediates NAc and social development during sex-specific adolescent periods and via sex-specific synaptic pruning targets. In this report, we demonstrate that interrupting microglial pruning in NAc during adolescence persistently dysregulates social behavior towards a familiar, but not novel social partner in both sexes, via sex-specific behavioral expression. This leads us to infer that naturally occurring NAc pruning serves to reduce social behaviors primarily directed toward a familiar conspecific in both sexes, but in sex-specific ways.

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