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- W3005258595 abstract "Astrocytes are crucial regulators of neuronal synapse development and function. In the rodent cortex neurons are arranged in layers, each with stereotyped synaptic connectivity. Cortical astrocytes produce several synapse promoting factors, however, whether they differentially regulate formation of synapses in different layers is unknown. Furthermore, the developmental expression pattern of astrocyte synaptogenic cues, and whether expression is regulated by neuronal or astrocyte activity, is unknown. Here we use genetic mouse models, immunohistochemistry and in situ hybridization to quantify the developmental expression changes of astrocyte-derived synapse promoting genes, such as glypicans and chordin like1, in the mouse visual cortex. The observed expression changes occurred mainly between post-natal days (P) 7 and 14, a time between synapse initiation and maturation, and showed layer specific regulation. For example, glypican4 expression is strongly reduced at P14 in layer (L) 1, while glypican6 expression is increased in deeper layers. Next, perturbing glutamate release from thalamic neurons by knocking out VGlut2 resulted in significant increase in glypican4 expression in L1, while expression of glypican6 decreased in deep layers. Moreover, perturbing astrocyte activity by knocking out IP3R2 resulted in a significant decrease in glypican4 expression, but had no effect on glypican6 expression. Remarkably, neuronal GluA1 AMPAR protein levels in L1 showed correlated expression changes to glypican4 in both neuronal, and astrocyte activity perturbed mice models. To determine the underlying mechanism of astrocyte gene regulation by neuronal and astrocyte activity I have conducted single cell transcriptomic profiling of astrocytes in each of the models. These findings provide insight into neuron-astrocyte interaction as it occurs at the level of the distinct cortical connections, and constitute an important frame work for future studies of astrocyte and synapse development in the cortex." @default.
- W3005258595 created "2020-02-14" @default.
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- W3005258595 date "2020-02-01" @default.
- W3005258595 modified "2023-09-26" @default.
- W3005258595 title "Astrocyte Expression of Synapse Promoting Genes is Developmentally Regulated by Neuronal and Astrocyte Activity" @default.
- W3005258595 doi "https://doi.org/10.1016/j.bpj.2019.11.330" @default.
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