Use-dependent increases in glutamate concentration activate presynaptic metabotropic glutamate receptors

The classical view of fast chemical synaptic transmission is that released neurotransmitter acts locally on postsynaptic receptors and is cleared from the synaptic cleft within a few milliseconds by diffusion and by specific reuptake mechanisms. This rapid clearance restricts the spread of neurotran...

Full description

Saved in:
Bibliographic Details
Published in:Nature (London) 1997-02, Vol.385 (6617), p.630-634
Main Authors: Scanziani, Massimo, Salin, Paul A, Vogt, Kaspar E, Malenka, Robert C, Nicoll, Roger A
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Brain
Central nervous system
Central neurotransmission. Neuromudulation. Pathways and receptors
Evoked Potentials
Excitatory Amino Acid Antagonists - pharmacology
Fundamental and applied biological sciences. Psychology
Glutamates - metabolism
Guinea Pigs
Hippocampus - metabolism
In Vitro Techniques
Molecular biology
Neurology
Pimelic Acids - pharmacology
Quinoxalines - pharmacology
Receptors, AMPA - antagonists & inhibitors
Receptors, AMPA - metabolism
Receptors, Metabotropic Glutamate - antagonists & inhibitors
Receptors, Metabotropic Glutamate - metabolism
Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors
Receptors, N-Methyl-D-Aspartate - metabolism
Synapses - metabolism
Vertebrates: nervous system and sense organs
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The classical view of fast chemical synaptic transmission is that released neurotransmitter acts locally on postsynaptic receptors and is cleared from the synaptic cleft within a few milliseconds by diffusion and by specific reuptake mechanisms. This rapid clearance restricts the spread of neurotransmitter and, combined with the low affinities of many ionotropic receptors, ensures that synaptic transmission occurs in a point-to-point fashion. We now show, however, that when transmitter release is enhanced at hippocampal mossy fibre synapses, the concentration of glutamate increases and its clearance is delayed; this allows it to spread away from the synapse and to activate presynaptic inhibitory metabotropic glutamate receptors (mGluRs). At normal levels of glutamate release during low-frequency activity, these presynaptic receptors are not activated. When glutamate concentration is increased by higher-frequency activity or by blocking glutamate uptake, however, these receptors become activated, leading to a rapid inhibition of transmitter release. This effect may be related to the long-term depression of mossy fibre synaptic responses that has recently been shown after prolonged activation of presynaptic mGluRs (refs 2, 3). The use-dependent activation of presynaptic mGluRs that we describe here thus represents a negative feedback mechanism for controlling the strength of synaptic transmission.
ISSN:0028-0836
1476-4687
DOI:10.1038/385630a0