Membrane Ca2+ permeability and IP3R2 dependent Ca2+-induced Ca2+ release are essential for astrocytic intracellular Ca2+ elevation upon neuronal stimulation at the mouse hippocampal CA3 - CA1 excitatory synapses

Astrocytes are intricately involved in the activity of neural circuits, however, their basic physiology of interacting with neurons remains controversial. Using dual-indicator two-photon imaging of neurons and astrocytes during stimulations of hippocampal CA3 - CA1 Schaffer collateral (Scc) excitatory synapses, we report that under physiological conditions, the increased glutamate released from the higher frequency stimulation of neurons can accelerate local astrocytic Ca2+ levels. As consequences of extracellular glutamate clearance and maintaining of astrocytic intracellular Na+ homeostasis, the increase of astrocytic membrane Ca2+ permeability via Na+/Ca2+ exchanger (NCX) reverse mode is the primary reason of eliciting astrocytic intracellular Ca2+ elevation upon neuronal stimulation. This Ca2+-induced Ca2+ release is dependent on inositol triphosphate receptor type 2 (IP3R2). In addition, ATP released from Scc excitatory synapses can contribute to this molecular mechanism of Ca2+-induced Ca2+ release in astrocytes.