Presynaptic group 1 metabotropic glutamate receptors may contribute to the expression of long-term potentiation in the hippocampal CA1 region.
In this study, we investigated the possible contribution of presynaptic group 1 metabotropic glutamate receptor activation to changes in synaptic efficacy by means of analysis of glutamate release in hippocampal synaptosomes. Data were interpreted in the context of group 1 metabotropic glutamate receptor involvement in synaptic plasticity in the CA1 region of freely moving rats. In synaptosomes, 3,5-dihydroxyphenylglycine enhanced diacylglycerol formation and facilitated vesicular Ca(2+)-dependent glutamate release, whereas trans-azetidine-2,4-dicarboxylic acid had no effect on these processes. Trans-azetidine-2,4-dicarboxylic acid enhanced glutamate release, but in a Ca(2+)-independent manner. This effect was mimicked by the L-glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid. (R,S)-alpha-Methyl-4-carboxyphenylglycine blocked the effects of 3,5-dihydroxyphenylglycine, but not trans-azetidine-2,4-dicarboxylic acid in synaptosomes. Short-term potentiation (100 Hz, three bursts of 10 stimuli, 0.1 ms stimulus duration, 10 s interburst interval) was induced in the CA1 region in vivo. The metabotropic glutamate receptor agonist 1S,3R-aminocyclopentane-2,3-dicarboxylic acid, or the group 1 metabotropic glutamate receptor agonists, 3,5-dihydroxyphenylglycine and trans-azetidine-2,4-dicarboxylic acid, dose-dependently facilitated short-term potentiation into long-term potentiation, which lasted > 24 h. The facilitation was inhibited by the metabotropic glutamate receptor antagonist, (R,S)-alpha-methyl-4-carboxyphenylglycine, and the group 1 metabotropic glutamate receptor antagonist, (S)-4-carboxy-phenylglycine, but not by the group 2 metabotropic glutamate receptor antagonist, (R,S)-alpha-methylserine-O-phosphate monophenyl ester. L-Trans-pyrrolidine-2,4-dicarboxylic acid dose-dependently facilitated short-term potentiation into long-term potentiation, which lasted < 4 h. These data suggest that activation of group 1 metabotropic glutamate receptors results in presynaptic modulation of glutamate release. This effect may contribute to group 1 metabotropic glutamate modulation of the expression of long-term potentiation in vivo.
Manahan-Vaughan
D
D
Leibniz Institute for Neurobiology, Department of Neurophysiology, Magdeburg, Germany. manahan@ifn-magdeburg.de
Herrero
I
I
Reymann
K G
KG
Sánchez-Prieto
J
J
D000818:Animals; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004075:Diglycerides / Q000378:metabolism; D004558:Electric Stimulation; D004569:Electroencephalography; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000737:chemistry* / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000737:chemistry* / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D012118:Resorcinols / Q000494:pharmacology; D013574:Synaptosomes / Q000737:chemistry / Q000378:metabolism
D003998:Dicarboxylic Acids; D004075:Diglycerides; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D014179:Neurotransmitter Uptake Inhibitors; D011759:Pyrrolidines; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C083095:azetidine-2,4-dicarboxylic acid; D018698:Glutamic Acid; D001383:Azetidinecarboxylic Acid; C079215:3,5-dihydroxyphenylglycine; C083486:pyrrolidine-2,4-dicarboxylic acid; D002118:Calcium; D005998:Glycine