Neuroglial Interactions in Cerebral Physiology and Pathologies, Center for Interdisciplinary Research in Biology, College de France, CNRS, Inserm, Labex Memolife, Université PSL, Paris, France.
Theranexus, Lyon, France.
PLoS Biol. 2023 Apr 11;21(4):e3002075. doi: 10.1371/journal.pbio.3002075. eCollection 2023 Apr.
Astrocytes crucially contribute to synaptic physiology and information processing. One of their key characteristics is to express high levels of connexins (Cxs), the gap junction-forming protein. Among them, Cx30 displays specific properties since it is postnatally expressed and dynamically upregulated by neuronal activity and modulates cognitive processes by shaping synaptic and network activities, as recently shown in knockout mice. However, it remains unknown whether local and selective upregulation of Cx30 in postnatal astrocytes within a physiological range modulates neuronal activities in the hippocampus. We here show in mice that, whereas Cx30 upregulation increases the connectivity of astroglial networks, it decreases spontaneous and evoked synaptic transmission. This effect results from a reduced neuronal excitability and translates into an alteration in the induction of synaptic plasticity and an in vivo impairment in learning processes. Altogether, these results suggest that astroglial networks have a physiologically optimized size to appropriately regulate neuronal functions.
星形胶质细胞对突触生理学和信息处理有至关重要的贡献。它们的一个关键特征是表达高水平的连接蛋白（Cxs），即间隙连接形成蛋白。其中，Cx30 表现出特定的性质，因为它在出生后表达，并被神经元活动动态上调，最近在敲除小鼠中显示出调节认知过程的作用，通过塑造突触和网络活动。然而，目前尚不清楚在生理范围内局部和选择性地上调出生后星形胶质细胞中的 Cx30 是否会调节海马体中的神经元活动。我们在小鼠中表明，尽管 Cx30 的上调增加了星形胶质细胞网络的连接性，但它会降低自发和诱发的突触传递。这种效应源于神经元兴奋性的降低，并转化为突触可塑性的诱导改变以及体内学习过程的损伤。总的来说，这些结果表明星形胶质细胞网络具有生理上优化的大小，以适当调节神经元功能。
