Role of astrocytic signaling in excitatory synapse formation, maturation, and function during cortical development: implications for neurodevelopmental disorders
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Astrocytes are the most numerous glial cell types in the CNS. These cells are able to receive signals from microglia and synapses via the G protein-coupled receptors (GPCRs) on their surface, and are in a unique position to signal back to neurons and microglia. Astrocytes are also known to play critical roles in the progression and maintenance of brain inflammation by responding to and producing inflammatory mediators. Furthermore, there is accumulating evidence that postnatal inflammation during brain development is involved in the etiology of major neurodevelopmental psychiatric diseases, including autism and schizophrenia. We hypothesize that abnormal activation of astrocytic Gs GPCR signaling during brain development triggers the production and release of pro-inflammatory molecules and/or synaptogenic, maturation or pruning factors to alter excitatory synaptic transmission. To test this hypothesis, we are using chemogenetic approach to selectively activate astrocytic Gs GPCR signaling in the developing mouse primary visual cortex (V1) as a model system.