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 are 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.

中文翻译：

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星形胶质细胞突触调节基因的活性依赖性调节

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因素尚不清楚。我们确定了发育中的小鼠视觉皮层中星形胶质细胞突触调节基因的表达谱，确定了显示差异时间和层丰富表达的星形胶质细胞信号。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，因为它们在缺乏从丘脑皮质末端释放谷氨酸的小鼠中不存在。因此，突触仍然不成熟。当星形胶质细胞信号通过减少星形胶质细胞储存的钙释放而减弱时，突触调节基因的表达和突触发育也会改变。单核 RNA 测序确定了由神经元和星形胶质细胞活动调节的星形胶质细胞基因组，以及显示特定层富集的基因盒。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，突出了星形胶质细胞作为在神经发育障碍中操纵的目标。