核团星形胶质细胞双向调节社交行为

Jonathan W VanRyzin, Kathryn J Reissner
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摘要

社交行为对物种的生存和繁衍至关重要,而不适应的社交行为往往与神经发育和精神疾病有关。因此,驱动社会行为的神经回路和细胞机制为健康和疾病的关键过程提供了信息。尤其是,脑内凹凸核(NAc)是整合社会和非社会信息的关键枢纽,这些信息是成功的社会交往和奖励动机行为所必需的。虽然 NAc 内的星形胶质细胞在调节神经活动方面的作用已得到公认,但它们对社交行为的影响尚未明确。为了解决这个问题,我们操纵了 NAc 星形胶质细胞信号传导,并确定了其对社会交往的影响。NAc 核心星形胶质细胞会双向影响大鼠的社会行为;激动星形胶质细胞特异性 hM3D(Gq) DREADD 受体会增加社会互动测试中的社会互动时间,并增加三室测试中的社会偏好。相反,通过病毒表达 hPMCA 来减少星形胶质细胞内的钙信号传导,则会减少这些测试中的社会互动和社会偏好。这些结果表明,NAc 星形胶质细胞积极参与了社会行为的调节,并强调了星形胶质细胞在以社会功能障碍为特征的疾病中可能扮演的角色。
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Nucleus accumbens astrocytes bidirectionally modulate social behavior
Social behaviors are critical for survival and fitness of a species, and maladaptive social behaviors are frequently associated with neurodevelopmental and psychiatric disorders. As such, the neural circuits and cellular mechanisms driving social behaviors inform critical processes contributing to both health and disease. In particular, the nucleus accumbens (NAc) is a key hub for the integration of both social and non-social information required for successful social interactions and reward motivated behaviors. While astrocytes within the NAc have a recognized role in modulating neural activity, their influence over social behavior is yet undefined. To address this question, we manipulated NAc astrocyte signaling and determined effects on social interactions. NAc core astrocytes bidirectionally influenced social behavior in rats; agonism of astrocyte-specific hM3D(Gq) DREADD receptors increased social interaction time in the social interaction test and increased social preference in the 3-chamber test. Conversely, decreasing intracellular calcium signaling in astrocytes with viral expression of hPMCA reduced both social interaction and social preference in these tests. These results suggest that NAc astrocytes actively participate in the regulation of social behavior and highlight a putative role for astrocytes in disorders characterized by social dysfunction.
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