Deriving the glutamate clearance time course from transporter currents in CA1 hippocampal astrocytes: transmitter uptake gets faster during development.
At many excitatory synapses, the neurotransmitter glutamate diffuses beyond the synaptic cleft to activate extrasynaptic targets. The extent and impact of such transmitter "spillover" on the processing capacity of neuronal networks are unclear, in part because it remains unknown how far transmitter diffuses from its point of release before being removed from the extracellular space by high-affinity glutamate transporters. Synaptically activated, transporter-mediated currents (STCs) recorded in hippocampal astrocytes provide an experimental measure of glutamate uptake, but the time course of the STC may be shaped, or "filtered," by other factors and therefore not represent a direct indication of clearance rate. Here, STCs were recorded from astrocytes in rat hippocampal slices under conditions in which uptake capacity was reduced and the STC decay reflected a slowed rate of glutamate clearance. The temporal characteristics of the filtering mechanisms were extracted from these responses, and the glutamate clearance time course in control conditions was derived. The results indicate that glutamate can be cleared from the extrasynaptic space within 1 ms. Clearance is fastest in adult neuropil, corresponding to a developmental increase in glial transporter expression. Synaptically released glutamate is taken up at the same rate as glutamate released via flash photolysis, indicating that the spatial location of transporters relative to the site of glutamate release does not affect the time course of clearance. Slower clearance in young animals would permit glutamate to diffuse greater distances, indicating a particularly important role for extrasynaptic receptors early in development.
Diamond
Jeffrey S
JS
Synaptic Physiology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-3701, USA. diamondj@ninds.nih.gov
D000367:Age Factors; D027322:Amino Acid Transport System X-AG / Q000037:antagonists & inhibitors; D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000494:pharmacology; D001253:Astrocytes / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology* / Q000254:growth & development; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D010852:Picrotoxin / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D054830:Sesterterpenes; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D013997:Time Factors
D027322:Amino Acid Transport System X-AG; D001224:Aspartic Acid; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D018698:Glutamic Acid; D010852:Picrotoxin; D054830:Sesterterpenes; C082764:alpha-(4,5-dimethoxy-2-nitrobenzyl) glutamate; C120673:benzyloxyaspartate; C022961:picrotoxinin