小柯机器人

美国贝勒医学院Benjamin Deneen团队发现，抑制性输入通过胶质GABA_BR指导星形细胞的形态发生。相关论文于2023年4月26日在线发表在《自然》杂志上。

研究人员表明，抑制性神经元的活动对星形细胞的形态发生是必要的和充分的。研究人员发现，来自抑制性神经元的输入通过星形细胞的GABA_B受体（GABA_BR）发挥作用，其在星形细胞中的缺失会导致一系列脑区的形态复杂性的丧失和电路功能的破坏。GABA_BR在发育中的星形细胞中的表达是由SOX9或NFIA以区域特异性方式调节的，这些转录因子的缺失导致星形细胞形态发生的区域特异性缺陷，这是由与表现出区域限制性表达模式的转录因子的相互作用赋予的。总之，这项研究确定来自抑制性神经元和星形细胞GABA_BR的输入是形态发生的普遍调节因素，同时进一步揭示了星形细胞发育的区域特异性转录依赖性的组合代码，它与活动依赖性过程交织在一起。

据了解，神经元和胶质细胞之间的交流在建立和维持高阶大脑功能方面具有重要作用。星形胶质细胞被赋予了复杂的形态，使其外围过程与神经元突触接近，直接促进了其对大脑回路的调节。最近的研究表明，兴奋性神经元活动促进少突胶质细胞的分化；抑制性神经传递是否在发育过程中调节星形胶质细胞的形态发生尚不清楚。

附：英文原文

Title: Inhibitory input directs astrocyte morphogenesis through glial GABABR

Author: Cheng, Yi-Ting, Luna-Figueroa, Estefania, Woo, Junsung, Chen, Hsiao-Chi, Lee, Zhung-Fu, Harmanci, Akdes Serin, Deneen, Benjamin

Issue&Volume: 2023-04-26

Abstract: Communication between neurons and glia has an important role in establishing and maintaining higher-order brain function1. Astrocytes are endowed with complex morphologies, placing their peripheral processes in close proximity to neuronal synapses and directly contributing to their regulation of brain circuits2,3,4. Recent studies have shown that excitatory neuronal activity promotes oligodendrocyte differentiation5,6,7; whether inhibitory neurotransmission regulates astrocyte morphogenesis during development is unclear. Here we show that inhibitory neuron activity is necessary and sufficient for astrocyte morphogenesis. We found that input from inhibitory neurons functions through astrocytic GABAB receptor (GABABR) and that its deletion in astrocytes results in a loss of morphological complexity across a host of brain regions and disruption of circuit function. Expression of GABABR in developing astrocytes is regulated in a region-specific manner by SOX9 or NFIA and deletion of these transcription factors results in region-specific defects in astrocyte morphogenesis, which is conferred by interactions with transcription factors exhibiting region-restricted patterns of expression. Together, our studies identify input from inhibitory neurons and astrocytic GABABR as universal regulators of morphogenesis, while further revealing a combinatorial code of region-specific transcriptional dependencies for astrocyte development that is intertwined with activity-dependent processes.

DOI: 10.1038/s41586-023-06010-x

Source: https://www.nature.com/articles/s41586-023-06010-x

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
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