PDF(Pubmed)
Abstract：
The links between early life stress (ELS) and the emergence of psychopathology such as increased anxiety and depression are now well established, although the specific neurobiological and developmental mechanisms that translate ELS into poor health outcomes are still unclear. The consequences of ELS are complex because they depend on the form and severity of early stress, duration, and age of exposure as well as co-occurrence with other forms of physical or psychological trauma. The long term effects of ELS on the corticolimbic circuit underlying emotional and social behavior are particularly salient because ELS occurs during critical developmental periods in the establishment of this circuit, its local balance of inhibition:excitation and its connections with other neuronal pathways. Using examples drawn from the human and rodent literature, we review some of the consequences of ELS on the development of the corticolimbic circuit and how it might impact fear regulation in a sex- and hemispheric-dependent manner in both humans and rodents. We explore the effects of ELS on local inhibitory neurons and the formation of perineuronal nets (PNNs) that terminate critical periods of plasticity and promote the formation of stable local networks. Overall, the bulk of ELS studies report transient and/or long lasting alterations in both glutamatergic circuits and local inhibitory interneurons (INs) and their associated PNNs. Since the activity of INs plays a key role in the maturation of cortical regions and the formation of local field potentials, alterations in these INs triggered by ELS might critically participate in the development of psychiatric disorders in adulthood, including impaired fear extinction and anxiety behavior.
摘要：
早期生活压力（ELS）和精神病理学的出现之间的联系，如焦虑和抑郁的增加，现在已经确立。尽管将ELS转化为不良健康结局的具体神经生物学和发育机制仍不清楚.ELS的后果是复杂的，因为它们取决于早期压力的形式和严重程度，持续时间,和暴露年龄以及与其他形式的身体或心理创伤的共同发生。ELS对情感和社会行为基础上的皮质边缘回路的长期影响特别突出，因为ELS发生在该回路建立的关键发育时期，抑制的局部平衡：兴奋及其与其他神经元通路的联系。利用人类和啮齿动物文献中的例子，我们回顾了ELS对皮质边缘回路发展的一些影响,以及它如何以性别和半球依赖性方式影响人类和啮齿动物的恐惧调节.我们探讨了ELS对局部抑制性神经元和神经周网络（PNN）形成的影响，这些网络终止了可塑性的关键时期并促进了稳定的本地网络的形成。总的来说,大部分ELS研究报告了谷氨酸能回路和局部抑制性中间神经元(INs)及其相关PNN的短暂和/或持久改变.由于INs的活动在皮层区域的成熟和局部场电位的形成中起着关键作用，由ELS引发的这些INs的改变可能严重参与成年期精神疾病的发展，包括受损的恐惧灭绝和焦虑行为。
