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Mechanisms governing activity-dependent synaptic pruning in the developing mammalian CNS
Nature Reviews Neuroscience ( IF 28.7 ) Pub Date : 2021-09-20 , DOI: 10.1038/s41583-021-00507-y
Travis E Faust 1 , Georgia Gunner 1 , Dorothy P Schafer 1
Affiliation  

Almost 60 years have passed since the initial discovery by Hubel and Wiesel that changes in neuronal activity can elicit developmental rewiring of the central nervous system (CNS). Over this period, we have gained a more comprehensive picture of how both spontaneous neural activity and sensory experience-induced changes in neuronal activity guide CNS circuit development. Here we review activity-dependent synaptic pruning in the mammalian CNS, which we define as the removal of a subset of synapses, while others are maintained, in response to changes in neural activity in the developing nervous system. We discuss the mounting evidence that immune and cell-death molecules are important mechanistic links by which changes in neural activity guide the pruning of specific synapses, emphasizing the role of glial cells in this process. Finally, we discuss how these developmental pruning programmes may go awry in neurodevelopmental disorders of the human CNS, focusing on autism spectrum disorder and schizophrenia. Together, our aim is to give an overview of how the field of activity-dependent pruning research has evolved, led to exciting new questions and guided the identification of new, therapeutically relevant mechanisms that result in aberrant circuit development in neurodevelopmental disorders.



中文翻译:

发育中哺乳动物中枢神经系统活动依赖性突触修剪的机制

自从 Hubel 和 Wiesel 最初发现神经元活动的变化可以引起中枢神经系统 (CNS) 的发育重新布线以来,已经过去了将近 60 年。在此期间,我们对自发神经活动和感觉体验诱导的神经元活动变化如何引导 CNS 回路发展有了更全面的了解。在这里,我们回顾了哺乳动物中枢神经系统中依赖于活动的突触修剪,我们将其定义为去除突触的一个子集,同时保留其他突触,以响应发育中的神经系统中神经活动的变化。我们讨论了越来越多的证据表明免疫和细胞死亡分子是重要的机制联系,神经活动的变化通过这些联系指导特定突触的修剪,强调神经胶质细胞在此过程中的作用。最后,我们讨论了这些发育修剪程序如何在人类中枢神经系统的神经发育障碍中出错,重点是自闭症谱系障碍和精神分裂症。总之,我们的目标是概述活动依赖性修剪研究领域是如何演变的,如何引发令人兴奋的新问题,并指导识别新的、治疗相关的机制,这些机制会导致神经发育障碍的异常回路发育。

更新日期:2021-09-20
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