Ca2+ signaling in astrocytes from Ip3r2−/− mice in brain slices and during startle responses in vivo.

Intracellular Ca²⁺ signaling is considered to be important for multiple astrocyte functions in neural circuits. However, mice devoid of inositol triphosphate type 2 receptors (IP3R2) reportedly lack all astrocyte Ca²⁺ signaling, but display no neuronal or neurovascular deficits, implying that astrocyte Ca²⁺ fluctuations are not involved in these functions. An assumption has been that the loss of somatic Ca²⁺ fluctuations also reflects a similar loss in astrocyte processes. We tested this assumption and found diverse types of Ca²⁺ fluctuations in astrocytes, with most occurring in processes rather than in somata. These fluctuations were preserved in Ip3r2^−/− (also known as Itpr2^−/−) mice in brain slices and in vivo, occurred in end feet, and were increased by G protein-coupled receptor activation and by startle-induced neuromodulatory responses. Our data reveal previously unknown Ca²⁺ fluctuations in astrocytes and highlight limitations of studies that used Ip3r2^−/− mice to evaluate astrocyte contributions to neural circuit function and mouse behavior. [ABSTRACT FROM AUTHOR]