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星形胶质细胞关闭运动回路的关键期。

Astrocytes close a motor circuit critical period.

机构信息

Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregon, Eugene, OR, USA.

Kennedy Center, Department of Pediatrics, The University of Chicago, Chicago, IL, USA.

出版信息

Nature. 2021 Apr;592(7854):414-420. doi: 10.1038/s41586-021-03441-2. Epub 2021 Apr 7.

Abstract

Critical periods-brief intervals during which neural circuits can be modified by activity-are necessary for proper neural circuit assembly. Extended critical periods are associated with neurodevelopmental disorders; however, the mechanisms that ensure timely critical period closure remain poorly understood. Here we define a critical period in a developing Drosophila motor circuit and identify astrocytes as essential for proper critical period termination. During the critical period, changes in activity regulate dendrite length, complexity and connectivity of motor neurons. Astrocytes invaded the neuropil just before critical period closure, and astrocyte ablation prolonged the critical period. Finally, we used a genetic screen to identify astrocyte-motor neuron signalling pathways that close the critical period, including Neuroligin-Neurexin signalling. Reduced signalling destabilized dendritic microtubules, increased dendrite dynamicity and impaired locomotor behaviour, underscoring the importance of critical period closure. Previous work defined astroglia as regulators of plasticity at individual synapses; we show here that astrocytes also regulate motor circuit critical period closure to ensure proper locomotor behaviour.

摘要

关键期——神经回路可以通过活动进行修饰的短暂间隔——对于适当的神经回路组装是必要的。延长的关键期与神经发育障碍有关;然而,确保关键期及时关闭的机制仍知之甚少。在这里,我们定义了一个发育中的果蝇运动回路中的关键期,并确定星形胶质细胞对于适当的关键期终止是必不可少的。在关键期内,活动的变化调节运动神经元的树突长度、复杂性和连接性。星形胶质细胞在关键期结束前侵入神经丛,星形胶质细胞消融延长了关键期。最后,我们使用遗传筛选来识别关闭关键期的星形胶质细胞-运动神经元信号通路,包括神经连接素-神经递质信号。信号的减少使树突微管不稳定,增加了树突的动态性,并损害了运动行为,突出了关键期关闭的重要性。以前的工作将星形胶质细胞定义为单个突触可塑性的调节者;我们在这里表明,星形胶质细胞还调节运动回路的关键期关闭,以确保适当的运动行为。

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Astrocytes close a motor circuit critical period.星形胶质细胞关闭运动回路的关键期。
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