EXTRASYNAPTIC GLUTAMATE DIFFUSION IN THE HIPPOCAMPUS - ULTRASTRUCTURAL CONSTRAINTS, UPTAKE, AND RECEPTOR ACTIVATION

Citation
Da. Rusakov et Dm. Kullmann, EXTRASYNAPTIC GLUTAMATE DIFFUSION IN THE HIPPOCAMPUS - ULTRASTRUCTURAL CONSTRAINTS, UPTAKE, AND RECEPTOR ACTIVATION, The Journal of neuroscience, 18(9), 1998, pp. 3158-3170
Citations number
61
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences
Journal title
ISSN journal
0270-6474
Volume
18
Issue
9
Year of publication
1998
Pages
3158 - 3170
Database
ISI
SICI code
0270-6474(1998)18:9<3158:EGDITH>2.0.ZU;2-W
Abstract
Fast excitatory synapses are generally thought to act as private commu nication channels between presynaptic and postsynaptic neurons. Some r ecent findings, however, suggest that glutamate may diffuse out of the synaptic cleft and bind to several subtypes of receptors, either in t he perisynaptic membrane or at neighboring synapses. it is not known w hether activation of these receptors can occur in response to the rele ase of a single vesicle of glutamate. Here we estimate the spatiotempo ral profile of glutamate in the extrasynaptic space after vesicle exoc ytosis, guided by detailed ultrastructural measurements of the CA1 neu ropil in the adult rat. We argue that the vicinity of the synapse can be treated as an isotropic porous medium, in which diffusion is determ ined by the extracellular volume fraction and the tortuosity factor, a nd develop novel stereological methods to estimate these parameters. W e also estimate the spatial separation between synapses, to ask whethe r glutamate released at one synapse can activate NMDA and other high-a ffinity receptors at a neighboring synapse. Kinetic simulations of ext rasynaptic 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 synap se from its nearest neighbor is similar to 465 nm. Whether glutamate c an reach a sufficient concentration to activate NMDA receptors at this distance depends critically on the diffusion coefficient in the extra cellular space. If diffusion is much slower than in free aqueous solut ion, NMDA receptors could mediate crosstalk between neighboring synaps es.