Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Osaka University, Osaka, Japan.
Neuropsychopharmacology. 2022 Aug;47(9):1597-1607. doi: 10.1038/s41386-022-01358-6. Epub 2022 Jun 13.
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.
早期社交隔离与成年后的社交和情感问题有关。然而，社交剥夺如何损害社交和情感发展的神经机制还知之甚少。最近，眶额皮质 (OFC) 和基底外侧杏仁核 (BLA) 已被强调为社交和情感功能的关键节点。因此，我们假设早期社交剥夺会破坏 OFC-BLA 通路中的信息处理，导致社交和情感功能障碍。在这里，我们通过光遗传学和全细胞膜片钳方法检查了青春期社交隔离对成年小鼠 OFC-BLA 突触传递的影响。青春期社交隔离减少了成年后的社交偏好，并增加了被动应激应对行为。然后，我们检查了来自 OFC 的内侧或外侧亚区 (mOFC 或 lOFC) 到 BLA 的兴奋性突触传递。值得注意的是，青春期社交隔离降低了成年 mOFC-BLA 突触中的 AMPA/NMDA 比值，而 lOFC-BLA 突触中的比值增加。此外，我们在行为小鼠中光遗传学操纵 mOFC-BLA 或 lOFC-BLA 传递，并检查对社交和应激应对行为的影响。光遗传学操纵 mOFC-BLA 传递改变了社交行为而不影响被动应激应对行为，而光遗传学操纵 lOFC-BLA 传递改变了被动应激应对行为而不影响社交行为。我们的结果表明，青春期社交隔离诱导 mOFC-BLA 和 lOFC-BLA 突触中不同的突触后变化，这些变化可能分别导致社交和情感发育异常。
