Synaptic Signaling to a Separate Population?

Science Signaling  07 Oct 2008:
Vol. 1, Issue 40, pp. ec344
DOI: 10.1126/scisignal.140ec344

The tiny blips in postsynaptic membrane potential produced through the spontaneous release of individual quanta of neurotransmitter played a key role in elucidating the mechanisms underlying synaptic transmission, but the physiological importance of spontaneous release has remained unclear. Atasoy et al. provide evidence that spontaneous release of glutamate activates a population of postsynaptic N-methyl-D-aspartate receptors (NMDARs) distinct from those activated by evoked release. Using the use-dependent open channel NMDAR blocker MK-801 to determine NMDAR activation history, the authors looked for crosstalk between NMDARs activated by spontaneous or evoked release in dissociated cultures of rat hippocampal neurons, hippocampal slices, and autaptic synapses in solitary-neuron cultures. Whereas application of MK-801 to resting neurons rapidly blocked NMDAR-mediated miniature excitatory postsynaptic currents (NMDA-mEPSCs) resulting from spontaneous release, it had little effect on the NMDAR-mediated response to evoked release (NMDA-eEPSC). On the other hand, repeated stimulation in the presence of MK-801 led to a decrease in NMDA-eEPSC, whereas evoked release-dependent block had relatively little effect on subsequent NMDA-mEPSCs. Fluorescence imaging indicated that evoked and spontaneous release of synaptic vesicles frequently occurred at the same synapse, with little correlation between the rates of the two forms of release. Modeling suggested that, at medium to large synapses (>0.2 μm2 area), independent activation of two populations of NMDAR could occur. The authors propose that spontaneous and evoked release may activate different populations of NMDARs—even in the same synapse—an intriguing possibility that could enable these two forms of release to elicit distinct postsynaptic responses.

D. Atasoy, M. Ertunc, K. L. Moulder, J. Blackwell, C. Chung, J. Su, E. T. Kavalali, Spontaneous and evoked glutamate release activates two populations of NMDA receptors with limited overlap. J. Neurosci. 28, 10151-10166 (2008). [Abstract] [Full Text]