An analysis of glutamate spillover on the N-methyl-D-aspartate receptors at the cerebellar glomerulus

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Abstract
Glutamate spillover is thought to play a significant role in increasing neural transmission at the mossy fiber/granule cell cerebellar glomerulus. Glutamate spillover has been shown to activate AMPA receptors at the glomerulus, and here we complete the characterization of spillover at the glomerulus by investigating the role of glutamate spillover in N-methyl-D-aspartate receptor (NMDA-R) activation. We present a quantitative model of glutamate spillover combining recent models of glutamate diffusion and NMDA-R binding to determine the open probabilities of NMDA-Rs over time at a neighbor synapse. Simulation results from a baseline set of physiologically realistic parameters show that glutamate spillover onto a single neighbor synapse, created by glutamate that diffuses from a point source into a restricted fractional 2D-3D space and the glutamate concentration created by neighboring glutamate release sites, is sufficient to elicit an NMDA-R peak open probability of 0.23, approximately 79% of that obtained by a direct release (peak open probability of 0.29). Thus, it would appear that glutamate spillover at the glomerulus at NMDA receptors is even more substantial than that seen at AMPA receptors.