Vesicular release of glutamate mediates bidirectional signaling between astrocytes and neurons

Published on July 16, 2012 Reviewed on May 1, 2020   45 min

A selection of talks on Biochemistry

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0:00
My name is Vladimir Parpura and I will talk about bidirectional signaling between astrocytes and neurons mediated by the vesicular release of glutamate from these two major cellular components of the central nervous system.
0:16
Neuronal and astrocytic elements are in close structural association. In this electron micrograph, an astrocyte from the cerebellar cortex (colored in blue) is in close proximity to axonal terminals making synapses onto dendritic spines. Some of these synapses are engulfed by an astrocyte, while others are in partial contact with it. Such microanatomical arrangements are functionally referred to as a tripartite synapse, where in addition to the pre-synaptic and post-synaptic neural elements an astrocyte represents an additional component of a synapse. Tripartite synapses are not a phenomenon solely seen in the cerebellum, but are rather ubiquitously present throughout different regions of the central nervous system. This anatomical intimacy supports the idea that astrocytes are well positioned to respond to the neural signals, and to communicate to neurons as schematically presented in the next slide.
1:20
After the arrival of action potentials at the pre-synaptic terminal and opening of voltage-gated calcium channels, glutamate stored in synaptic vesicles is released into the synaptic cleft, and in turn signals to the post-synaptic neuron by acting on ionotropic and metabotropic receptors. A portion of the released glutamate can reach astrocytes surrounding the synapse, and that can stimulate their receptors, leading to an increase in astrocytic intracellular calcium levels. Additionally, glutamate can be taken up by astrocytes via plasma membrane glutamate transporters. The increase in intracellular calcium concentration in a single astrocyte can spread to adjacent astrocytes in the form of a wave of elevated calcium, a phenomenon predominantly mediated by the release of ATP, although extracellular glutamate at gap junctions also contributes to it. Through calcium-dependent exocytosis and vesicle release of glutamate, astrocytes can signal to neuronal pre-synaptic and post-synaptic sites. In this talk I'll limit discussion to glutamate-mediated bidirectional signaling as a consequence of exocytotic events in both cell types, using examples of initial discoveries, as summarized in the next slide. Effects of glutamate release from neurons and astrocytes are shown in A to C.

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Vesicular release of glutamate mediates bidirectional signaling between astrocytes and neurons

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