Disrupting cortical astrocyte Ca2+ signaling in developing brain induces social deficits and depressive‐like behaviors

Abstract Astrocytes are present throughout the central nervous system and display complex intracellular Ca 2+ signals. However, it is largely unknown regarding how astrocytic Ca 2+ signals regulate neural microcircuits in developing brain and mammalian behavior in vivo . In this study, we specifically overexpressed the plasma membrane calcium‐transporting ATPase2 (PMCA2) of cortical astrocytes and used immunohistochemistry, Ca 2+ imaging, electrophysiology, and behavioral tests to investigate the effects of genetically reducing cortical astrocyte Ca 2+ signaling during a critical developmental period in vivo . We found that reducing cortical astrocyte Ca 2+ signaling during development led to social interaction deficits, depressive‐like behaviors, and abnormal synaptic structure and transmission. In addition, restoring cortical astrocyte Ca 2+ signaling using chemogenetic activation of Gq‐coupled designer receptors exclusively activated by designer drugs rescued these synaptic and behavioral deficits. Together, our data demonstrate that the integrity of cortical astrocyte Ca 2+ signaling in developing mice is critical for neural circuit development and may be involved in the pathogenesis of developmental neuropsychiatric diseases, such as autism spectrum disorders and depression.