Reexamination of the effects of MCPG on hippocampal LTP, LTD, and depotentiation.
1. We examined the effects of the metabotropic glutamate receptor (mGluR) antagonist alpha-methyl-4-carboxyphenylglycine (MCPG) on the induction of long-term potentiation (LTP) long-term depression (LTD), and depotentiation in CA1 hippocampal neurons using extracellular recording techniques. 2. MCPG (500 microM) strongly antagonized the presynaptic inhibitory action of the mGluR agonist 1-aminocyclopentane-(1S,3R)-dicarboxylic acid yet failed to block LTP induced with either tetanic stimulation (100 Hz, 1 s) or theta-burst stimulation. 3. To test the possibility that our failure to block LTP was due to prior activation of a "molecular switch" that in its "on" state obviates the need for mGluR activation to generate LTP, we gave repeated periods of prolonged low-frequency stimulation (LFS; 1 Hz, 10 min), a manipulation reported to turn the switch "off." Although this stimulation saturated LTD, subsequent application of MCPG still failed to block LTP. 4. MCPG did not block LFS-induced depotentiation in older slices (4-6 wk) or LFS-induced LTD in older, young (11-18 days), or neonatal (3-7 days) slices. 5. These results demonstrate that MCPG-sensitive mGluRs are not necessary for the induction of LTP, LTD, or depotentiation in hippocampal CA1 pyramidal cells. The possibility remains, however, that their activation may modify the threshold for the induction of these long-term plastic changes.
D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects*; D009473:Neuronal Plasticity; D051381:Rats; D013997:Time Factors
D001565:Benzoates; D018691:Excitatory Amino Acid Antagonists; C079694:alpha-methyl-4-carboxyphenylglycine; D005998:Glycine