IP3R2-Mediated Astrocytic Ca Transients Are Critical to Sustain Modulatory Effects of Locomotion on Neurons in Mouse Somatosensory Cortex.

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 activity is through the release of Ca via the inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) from the endoplasmic reticulum (ER). Studies using IP3R2 knockout mouse models () have shown that eliminating IP3R2 leads to a significant reduction in astrocytic Ca activity However, there is ongoing controversy regarding the effect of this IP3R2-dependent reduction in astrocytic Ca transients on neuronal activity. In our study, we employed dual-color two-photon Ca imaging to study astrocytes and neurons simultaneously in vibrissa somatosensory cortex (vS1) in awake-behaving wild-type and mice. We systematically characterized and compared both recorded astrocytic and neuronal Ca activities in wild-type and mice during various animal behaviors, particularly during the transition period from stillness to locomotion. We report that vS1 astrocytic Ca elevation in both wild-type and 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 mice. Our study suggests a non-synaptic modulatory mechanism on functions of astrocytic IP3R2-dependent Ca transients to local neurons.