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Journal of Neuroscience, Vol 14, 5120-5130, Copyright © 1994 by Society for Neuroscience
Presynaptic depression of synaptic transmission mediated by activation of metabotropic glutamate receptors in rat neocortex
JP Burke and JJ Hablitz
Neurobiology Research Center, University of Alabama at Birmingham 35294.
Conventional intracellular recordings were obtained from layer II-III
neurons in adult rat neocortical brain slices. Excitatory and inhibitory
(I) postsynaptic potentials (PSPs) were evoked prior to and during bath
application of agonists and antagonists of metabotropic glutamate receptors
(mGluRs). In the presence of the selective mGluR agonist
1S,3R-1-aminocyclopentane-1,3- dicarboxylic acid (1S,3R-ACPD; 5- 200
microM), both excitatory and inhibitory components of the evoked PSPs were
reversibly reduced. PSPs were significantly, but less effectively,
decreased by L-2-amino-4-phosphonobutyric acid. Exposure to putative mGluR
antagonists, alpha-methyl-4-carboxyphenylglycine or L-
2-amino-3-phosphonopropionic acid, did not inhibit the 1S,3R-ACPD- mediated
effect. In the presence of 6,7-dinitroquinoxaline-2,3-dione and
D-2-amino-5-phosphonovaleric acid, 1S,3R-ACPD reversibly depressed directly
evoked neocortical IPSPs; however, quisqualic acid (1-10 microM) did not
mimic this effect. Analysis of spontaneous PSPs and paired-pulse
facilitation indicated a presynaptic locus of action for 1S,3R-ACPD at
mGluRs. These findings indicate that a specific mGluR subtype(s) may
modulate both excitatory and inhibitory synaptic transmission in the adult
rat neocortex via a presynaptic reduction of transmitter release.
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