Differential control of synaptic and ectopic vesicular release of glutamate.

Exocytosis of synaptic vesicles occurs not only at synaptic active zones but also at ectopic sites. Ectopic exocytosis provides a direct and rapid mechanism for neurons to communicate with glia that does not rely on transmitter spillover from the synaptic cleft. In the cerebellar cortex the processes of Bergmann glia cells encase synapses between presynaptic climbing fiber varicosities and postsynaptic Purkinje cell spines and express both AMPA receptors and electrogenic glutamate transporters. AMPA receptors expressed by Purkinje cells and Bergmann glia cells are activated predominantly by synaptic and ectopic release, respectively, and therefore can be used to compare the properties of the two release mechanisms. We report that vesicular release differs at synaptic and ectopic sites in the magnitude of short-term plasticity and the proportions of Ca2+ channel subtypes that trigger glutamate release. High-affinity glutamate transporter-mediated currents in Bergmann glia cells follow the rules of synaptic release more closely than the rules of ectopic release, indicating that the majority of glutamate is released from conventional synapses. On the other hand, ectopic release produces high-concentration glutamate transients at Bergmann glia cell membranes that are necessary to activate low-affinity AMPA receptors rapidly. Ectopic release may provide a geographical cue to guide Bergmann glia cell membranes to surround active synapses and ensure efficient uptake of glutamate that diffuses out of the synaptic cleft.