Аннотация
Fast excitatory synapses are generally thought to act as private communication
channels between presynaptic and postsynaptic neurons. Some recent
findings, however, suggest that glutamate may diffuse out of the
synaptic cleft and bind to several subtypes of receptors, either
in the perisynaptic membrane or at neighboring synapses. It is not
known whether activation of these receptors can occur in response
to the release of a single vesicle of glutamate. Here we estimate
the spatiotemporal profile of glutamate in the extrasynaptic space
after vesicle exocytosis, guided by detailed ultrastructural measurements
of the CA1 neuropil in the adult rat. We argue that the vicinity
of the synapse can be treated as an isotropic porous medium, in which
diffusion is determined by the extracellular volume fraction and
the tortuosity factor, and develop novel stereological methods to
estimate these parameters. We also estimate the spatial separation
between synapses, to ask whether glutamate released at one synapse
can activate NMDA and other high-affinity receptors at a neighboring
synapse. Kinetic simulations of extrasynaptic glutamate uptake show
that transporters rapidly reduce the free concentration of transmitter.
Exocytosis of a single vesicle is, however, sufficient to bind to
high-affinity receptors situated in the immediate perisynaptic space.
The distance separating a typical synapse from its nearest neighbor
is approximately 465 nm. Whether glutamate can reach a sufficient
concentration to activate NMDA receptors at this distance depends
critically on the diffusion coefficient in the extracellular space.
If diffusion is much slower than in free aqueous solution, NMDA receptors
could mediate crosstalk between neighboring synapses.
- 9547224
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