Shigetomi et al. now present convincing evidence that astrocytic glutamate release only sometimes stimulates neurons, which helps to explain previous results. In mouse hippocampal slices, the time course (but not the amplitude) of astrocytic calcium elevation differed when triggered by activation of different endogenous receptors: PAR-1 or P2Y1.
More importantly, only PAR-1 activation, which produced slower and longer-lasting calcium elevation, increased the frequency of slow inward currents in neurons. These currents are mediated by activation of extrasynaptic NMDA receptors. The authors' previous work suggests that PAR-1 and P2Y1 receptors activate different forms of glutamate exocytosis, which could explain the differential effects on neurons.
The results demonstrate that the mechanism and/or dynamics of calcium elevation is a critical determinant of whether subsequent glutamate release activates neuronal receptors.-Society for Neuroscience
