Two forms of astrocyte calcium excitability have distinct effects on NMDA receptor-mediated slow inward currents in pyramidal neurons

Astrocytes display excitability in the form of intracellular calcium concentration ([Ca2+](i)) increases, but the signaling impact of these for neurons remains debated and controversial. A key unresolved issue is whether astrocyte [Ca2+](i) elevations impact neurons or not. Here we report that in the CA1 region of the hippocampus, agonists of native P2Y(1) and PAR-1 receptors, which are preferentially expressed in astrocytes, equally elevated [Ca2+](i) levels without affecting the passive membrane properties of pyramidal neurons. However, under conditions chosen to isolate NMDA receptor responses, we found that activation of PAR-1 receptors led to the appearance of NMDA receptor-mediated slow inward currents (SICs) in pyramidal neurons. In stark contrast, activation of P2Y(1) receptors was ineffective in this regard. The PAR-1 receptor-mediated increased SICs were abolished by several strategies that selectively impaired astrocyte [Ca2+](i) excitability and function. Our studies therefore indicate that evoked astrocyte [Ca2+](i) transients are not a binary signal for interactions with neurons, and that astrocytes result in neuronal NMDA receptor-mediated SICs only when appropriately excited. The data thus provide a basis to rationalize recent contradictory data on astrocyte-neuron interactions.