Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, United States.
Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, United States.
Elife. 2021 Sep 8;10:e70514. doi: 10.7554/eLife.70514.
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.
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，是什么控制这些信号的区域和时间表达尚不清楚。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，鉴定出了在不同时间和层中表现出差异表达的星形胶质细胞信号。这些模式不是星形胶质细胞所固有的，而是由视觉诱发的神经元活动所调节的，因为在缺乏从丘脑皮质末梢释放谷氨酸的小鼠中，这些信号不存在。因此，突触仍然不成熟。当通过减少星形胶质细胞储存的钙释放来削弱星形胶质细胞信号时，突触调节基因的表达和突触发育也会发生改变。单细胞 RNA 测序鉴定了受神经元和星形胶质细胞活动调节的星形胶质细胞基因群，以及一组表现出层特异性富集的基因。因此，皮质回路的发育需要星形胶质细胞和神经元之间的协调信号，这凸显了星形胶质细胞作为神经发育障碍治疗靶点的重要性。
