Abstract
Accumulating studies have shown that astrocytes are essential for regulating neurons at both synaptic and circuit levels. The main mechanism of brain astrocytic intracellular Ca(2+) activity is through the release of Ca(2+) via the inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) from the endoplasmic reticulum (ER). Studies using IP3R2 knockout mouse models (Itpr2(-/-)) have shown that eliminating IP3R2 leads to a significant reduction in astrocytic Ca(2+) activity However, there is ongoing controversy regarding the effect of this IP3R2-dependent reduction in astrocytic Ca(2+) transients on neuronal activity. In our study, we employed dual-color two-photon Ca(2+) imaging to study astrocytes and neurons simultaneously in vibrissa somatosensory cortex (vS1) in awake-behaving wild-type and Itpr2(-/-) mice. We systematically characterized and compared both recorded astrocytic and neuronal Ca(2+) activities in wild-type and Itpr2(-/-) mice during various animal behaviors, particularly during the transition period from stillness to locomotion. We report that vS1 astrocytic Ca(2+) elevation in both wild-type and Itpr2(-/-) mice was significantly modulated by free whisking and locomotion. However, vS1 neurons were only significantly modulated by locomotion in wild-type mice, but not in Itpr2(-/-) mice. Our study suggests a non-synaptic modulatory mechanism on functions of astrocytic IP3R2-dependent Ca(2+) transients to local neurons.