Ca(2+) signaling in astrocytes from IP3R2(−)(/)(−) mice in brain slices and during startle responses in vivo

Intracellular Ca(2+) signaling is considered important for multiple astrocyte functions in neural circuits. However, mice devoid of inositol triphosphate type 2 receptors (IP3R2) reportedly lack all astrocyte Ca(2+) signaling, but display no neuronal or neurovascular deficits, implying that astrocyte Ca(2+) fluctuations play no role(s) in these functions. An assumption has been that loss of somatic Ca(2+) fluctuations also reflects similar loss within astrocyte processes. Here, we tested this assumption and found diverse types of Ca(2+) fluctuations within astrocytes, with most occurring within processes rather than in somata. These fluctuations were preserved in IP3R2(−)(/)(−) mice in brain slices and in vivo, occurred in endfeet, were increased by G-protein coupled receptor activation and by startle-induced neuromodulatory responses. Our data reveal novel Ca(2+) fluctuations within astrocytes and highlight limitations of studies that used IP3R2(−)(/)(−) mice to evaluate astrocyte contributions to neural circuit function and mouse behavior.