Increased membrane Ca permeability drives astrocytic Ca dynamics during neuronal stimulation at excitatory synapses.

Astrocytes are intricately involved in the activity of neural circuits; however, their basic physiology of interacting with nearby neurons is not well established. Using two-photon imaging of neurons and astrocytes during higher frequency stimulation of hippocampal CA3-CA1 Schaffer collateral (Scc) excitatory synapses, we could show that increasing levels of released glutamate accelerated local astrocytic Ca elevation. However, blockage of glutamate transporters did not abolish this astrocytic Ca response, suggesting that astrocytic Ca elevation is indirectly associated with an uptake of extracellular glutamate. However, during the astrocytic glutamate uptake, the Na /Ca exchanger (NCX) reverse mode was activated, and mediated extracellular Ca entry, thereby triggering the internal release of Ca . In addition, extracellular Ca entry via membrane P2X receptors further facilitated astrocytic Ca elevation via ATP binding. These findings suggest a novel mechanism of activity induced Ca permeability increases of astrocytic membranes, which drives astrocytic responses during neuronal stimulation of CA3-CA1 Scc excitatory synapses.