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 ([Ca(2+)](i)) increases, but the signaling impact of these for neurons remains debated and controversial. A key unresolved issue is whether astrocyte [Ca(2+)](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 [Ca(2+)](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 [Ca(2+)](i) excitability and function. Our studies therefore indicate that evoked astrocyte [Ca(2+)](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.
Shigetomi
Eiji
E
Departments of Physiology and Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, California 90095-1751, USA.
Bowser
David N
DN
Sofroniew
Michael V
MV
Khakh
Baljit S
BS
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D058910:Purinergic P2 Receptor Agonists; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D044463:Receptor, PAR-1 / Q000819:agonists / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
C546383:P2ry1 protein, mouse; D058910:Purinergic P2 Receptor Agonists; D044463:Receptor, PAR-1; D016194:Receptors, N-Methyl-D-Aspartate; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D018698:Glutamic Acid; D002118:Calcium