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Role of Extrasynaptic ReceptorsNeurotransmitter receptors are clustered at synapses where vesicular exocytosis produces high concentrations of transmitter resulting in effective receptor activation. However, many neurons also express receptors at extrasynaptic locations. Whether these extrasynaptic receptors are activated depends upon their proximity to exocytotic events, their affinity for transmitter, and the rapidity of transmitter clearance from extracellular space. Although there is evidence for diffusion or “spillover” of transmitter from synapses to extrasynaptic receptors, exocytosis from non-synaptic sites, i.e., ectopic release sites, would result in larger, faster transients of transmitter in the extrasynaptic space and more effective activation of extrasynaptic receptors than expected from the smaller, slower transients resulting from spillover.
The Jahr lab has focused on the glutamateric synapses between climbing fibers and Purkinje cells of the cerebellum. Each of these synapses is encased by processes from Bergmann glial cells which prevent cross-talk between adjacent synapses. To maintain this critical encasement, AMPA receptors expressed by the Bergmann glial cell must be activated by glutamate released from the climbing fiber. Given the high densities of glutamate transporters expressed by both the Bergmann glial cell itself and the Purkinje cell, it is unlikely that these low affinity, extrasynaptic AMPA receptors could be activated by glutamate diffusing out of the synapse. Jahr and his colleagues have found that the release that activates Bergmann glial AMPA receptors has different properties from that which occurs within the synapse. First, quantal events are recorded in both Bergmann glial cells and Purkinje cells but they do not occur simultaneously, indicating that they do not result from the same population of exocytotic events. Second, release monitored by the two cells has different dependencies on extracellular calcium concentration, intracellular calcium buffering, and calcium channel subtype. Third, the magnitude and duration of short-term plasticity of release onto the two cells are different. These findings are consistent with exocytotic events occurring both within the synaptic cleft and from ectopic sites. While information transfer between the climbing fiber and the Purkinje cell depends on release within the synaptic cleft, maintaining the isolation of this synapse by Bergmann glial processes is the sole province of ectopic release.
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