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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.
