Disrupted cortical function underlies behavior dysfunction due to social isolation
Disrupted cortical function underlies behavior dysfunction due to social isolation
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DOI：
10.1172/jci63060
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发表时间：
2012-07-01
影响因子：
15.9
通讯作者：
Takahashi, Takuya
中科院分区：
文献类型：
--
作者：
Miyazaki, Tomoyuki;Takase, Kenkichi;Takahashi, Takuya
童年早期的压力事件会对情绪和认知行为产生深远的终身影响。然而，应激影响新生儿脑回路形成的机制知之甚少。在这里，我们表明，新生儿的社会隔离破坏分子，细胞和电路发育过程，导致行为功能障碍。新生儿隔离防止长时程增强和经验依赖性突触运输的α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）受体通常发生在电路形成在啮齿动物桶皮质。AMPA受体运输的这种抑制是由应激糖皮质激素的增加介导的，并且与钙/钙调蛋白依赖性蛋白激酶II型（CaMKII）信号传导减少有关，导致皮质的晶须敏感性减弱。这些影响导致幼年动物胡须依赖行为的缺陷。这些结果表明，新生儿的社会隔离改变神经元的可塑性机制，并扰乱了正常的皮层回路的初步建立，这可能解释了新生儿应激的长期行为影响。
Stressful events during early childhood can have a profound lifelong influence on emotional and cognitive behaviors. However, the mechanisms by which stress affects neonatal brain circuit formation are poorly understood. Here, we show that neonatal social isolation disrupts molecular, cellular, and circuit developmental processes, leading to behavioral dysfunction. Neonatal isolation prevented long-term potentiation and experience-dependent synaptic trafficking of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors normally occurring during circuit formation in the rodent barrel cortex. This inhibition of AMPA receptor trafficking was mediated by an increase of the stress glucocorticoid hormone and was associated with reduced calcium/calmodulin-dependent protein kinase type II (CaMKII) signaling, resulting in attenuated whisker sensitivity at the cortex. These effects led to defects in whisker-dependent behavior in juvenile animals. These results indicate that neonatal social isolation alters neuronal plasticity mechanisms and perturbs the initial establishment of a normal cortical circuit, which potentially explains the long-lasting behavioral effects of neonatal stress.