Activity-dependent modulation of synapse-regulating genes in astrocytes.
Activity-dependent modulation of synapse-regulating genes in astrocytes.
复制标题
DOI：
10.7554/elife.70514
复制
发表时间：
2021-09-08
期刊：
影响因子：
7.7
通讯作者：
Allen NJ
中科院分区：
文献类型：
--
作者：
Farhy-Tselnicker I;Boisvert MM;Liu H;Dowling C;Erikson GA;Blanco-Suarez E;Farhy C;Shokhirev MN;Ecker JR;Allen NJ
星形胶质细胞通过多种信号调节神经元突触的形成和功能;然而，在发育过程中控制这些信号的区域和时间表达的是未知的。我们确定了星形胶质细胞突触调节基因在发育中的小鼠视皮层的表达谱，确定了星形胶质细胞信号，显示出不同的时间和层丰富的表达。这些模式不是星形胶质细胞固有的，而是由视觉诱发的神经元活动调节的，因为它们在缺乏丘脑皮质末端谷氨酸释放的小鼠中不存在。因此，突触仍然不成熟。当星形胶质细胞储存的钙释放减少而减弱星形胶质细胞信号传导时，突触调节基因的表达和突触发育也会改变。单核RNA测序鉴定了由神经元和星形胶质细胞活性调节的星形胶质细胞基因组，以及显示层特异性富集的基因盒。因此，皮质回路的发展需要星形胶质细胞和神经元之间的协调信号传导，突出星形胶质细胞作为神经发育障碍中操纵的靶点。
Astrocytes regulate the formation and function of neuronal synapses via multiple signals; however, what controls regional and temporal expression of these signals during development is unknown. We determined the expression profile of astrocyte synapse-regulating genes in the developing mouse visual cortex, identifying astrocyte signals that show differential temporal and layer-enriched expression. These patterns are not intrinsic to astrocytes, but regulated by visually evoked neuronal activity, as they are absent in mice lacking glutamate release from thalamocortical terminals. Consequently, synapses remain immature. Expression of synapse-regulating genes and synaptic development is also altered when astrocyte signaling is blunted by diminishing calcium release from astrocyte stores. Single-nucleus RNA sequencing identified groups of astrocytic genes regulated by neuronal and astrocyte activity, and a cassette of genes that show layer-specific enrichment. Thus, the development of cortical circuits requires coordinated signaling between astrocytes and neurons, highlighting astrocytes as a target to manipulate in neurodevelopmental disorders.