Biomedical subjects
Publications and source records attributed to Ko Matsui.
The basal pole of a cone photoreceptor is in close contact with hundreds of bipolar cell dendrites. The function and properties of these unconventional junctions are a long-standing mystery. In this issue of Neuron, DeVries and colleagues provide compelling evidence that glutamate release from a single quanta can diffuse to distant AMPA/KA receptors on these basal junctions to generate slow mEPSCs.
The accepted theory of vesicular release of neurotransmitter posits that only a single vesicle per synapse can fuse with the membrane following action potential invasion, and this exocytotic event is limited to the ultrastructurally defined presynaptic active zone. Neither of these dictums is universally true. At certain synapses, more than a single vesicle can be released per action potential, and there is growing evidence that neuronal exocytosis can occur from sites that are unremarkable in electron micrographs. The first discrepancy extends the dynamic range of synapses, whereas the second enables faster and more robust chemical transmission at sites distant from morphologically defined synapses. Taken together, these attributes expand the capabilities of cellular communication in the nervous system.
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.
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.
Exocytosis of synaptic vesicles is generally assumed to occur only at ultrastructurally defined presynaptic active zones. If release is restricted to these sites, receptors not located within the synaptic cleft must be activated by transmitter that diffuses out of the cleft or not be activated at all. Here we report that AMPA receptor-mediated quantal events resulting from climbing fiber release are observed in Bergmann glial cells in the cerebellar cortex. These quantal events are not coincident with quanta recorded in neighboring Purkinje cells which receive input from the same climbing fiber. As Bergmann glial membranes are excluded from the synaptic cleft, we propose that exocytosis can occur from climbing fiber release sites located directly across from Bergmann glial membranes. Such ectopic release may account for the majority of the Bergmann glial AMPA response evoked by climbing fiber stimulation.