High-concentration rapid transients of glutamate mediate neural-glial communication via ectopic release.

Until recently, communication from neurons to astrocytes was thought to be mediated by low-concentration transients of glutamate caused by spillover from the synaptic cleft. However, quantal events recorded in rat cerebellar Bergmann glial cells (BGs) have fast kinetics, comparable with those recorded in neurons. By combining outside-out patch recordings of BG AMPA receptors and quantitative electron microscopic analysis of glutamate receptor subunit 1 (GluR1) and GluR4 immunogold labeling measurements, at both the soma and membranes surrounding synapses, we estimate the absolute density of functional AMPA receptors. Using a kinetic model of BG AMPA receptors, we find that quantal events recorded in BGs are produced by high-concentration (approximately 1-1.5 mM), fast transients (approximately 0.5 ms decay) of glutamate, similar to transients within the synaptic cleft. Our results indicate that neural signaling to BGs is mediated by ectopic release of transmitter from presynaptic elements directly facing the BG membrane.