Adolescent social isolation induces distinct changes in the medial and lateral OFC-BLA synapse and social and emotional alterations in adult mice
Adolescent social isolation induces distinct changes in the medial and lateral OFC-BLA synapse and social and emotional alterations in adult mice
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DOI：
10.1038/s41386-022-01358-6
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发表时间：
2022-06
影响因子：
7.6
通讯作者：
Hiroshi Kuniishi;Yuko Nakatake;M. Sekiguchi;M. Yamada
中科院分区：
文献类型：
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作者：
Hiroshi Kuniishi;Yuko Nakatake;M. Sekiguchi;M. Yamada
早年的社会孤立与成年后的社会和情感问题有关。然而，社会剥夺如何损害社会和情感发展的神经机制尚不清楚。近年来，眼窝前额皮质（OFC）和基底外侧杏仁核（BLA）被认为是社会和情感功能的关键节点。因此，我们假设早期社会剥夺破坏了OFC-BLA通路的信息加工，导致社会和情感功能障碍。在此，我们通过光遗传学和全细胞膜片钳方法研究了青少年社会隔离对成年小鼠OFC-BLA突触传递的影响。青少年社会隔离降低了社会偏好，增加了成年后的被动压力应对行为。然后，我们检查了从OFC的内侧或外侧亚区（mOFC或lOFC）到BLA的兴奋性突触传输。值得注意的是，青少年社会隔离降低了成年期mOFC-BLA突触的AMPA/NMDA比值，而lOFC-BLA突触的AMPA/NMDA比值升高。此外，我们通过光遗传学方法控制mOFC-BLA或lOFC-BLA在行为小鼠中的传递，并研究其对社交和压力应对行为的影响。光基因操纵mOFC-BLA基因传递改变了社会行为，但不影响被动应激应对行为，而光基因操纵lOFC-BLA基因传递改变了被动应激应对行为，但不影响社会行为。我们的研究结果表明，青少年社会隔离导致mOFC-BLA和lOFC-BLA突触发生明显的突触后变化，这些变化可能分别导致社交和情感发展异常。
Early-life social isolation is associated with social and emotional problems in adulthood. However, neural mechanisms underlying how social deprivation impairs social and emotional development are poorly understood. Recently, the orbitofrontal cortex (OFC) and basolateral amygdala (BLA) have been highlighted as key nodes for social and emotional functions. Hence, we hypothesize that early social deprivation disrupts the information processing in the OFC-BLA pathway and leads to social and emotional dysfunction. Here, we examined the effects of adolescent social isolation on the OFC-BLA synaptic transmission by optogenetic and whole-cell patch-clamp methods in adult mice. Adolescent social isolation decreased social preference and increased passive stress-coping behaviour in adulthood. Then, we examined excitatory synaptic transmissions to BLA from medial or lateral subregions of the OFC (mOFC or lOFC). Notably, adolescent social isolation decreased the AMPA/NMDA ratio in the mOFC-BLA synapse in adulthood, while the ratio was increased in the lOFC-BLA synapse. Furthermore, we optogenetically manipulated the mOFC-BLA or lOFC-BLA transmission in behaving mice and examined the effects on social and stress-coping behaviours. Optogenetic manipulation of the mOFC-BLA transmission altered social behaviour without affecting passive stress-coping behaviour, while optogenetic manipulation of the lOFC-BLA transmission altered passive stress-coping behaviour without affecting social behaviour. Our results suggest that adolescent social isolation induces distinct postsynaptic changes in the mOFC-BLA and lOFC-BLA synapses, and these changes may separately contribute to abnormalities in social and emotional development.