Properties of a presynaptic metabotropic glutamate receptor in rat neostriatal slices.
1. The effect of the metabotropic glutamate receptor agonist trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD) on glutamatergic transmission at corticostriate synapses was examined using slices of neostriatum. Field potential recordings were performed in slices from adult animals, and the effects of t-ACPD on the synaptically driven population spike were examined. Tight-seal whole-cell recordings were made in slices from 2 to 4-wk-old rats, and effects of t-ACPD on the amplitude of excitatory postsynaptic potentials (EPSPs) and postsynaptic neuronal membrane properties were examined. In addition, the effects of putative metabotropic receptor agonists and antagonists and 4-aminopyridine were examined. The ability of these compounds to mimic t-ACPD or block its actions were determined. 2. Application of t-ACPD (5-100 microM) depressed the maximal amplitude of the synaptically driven population spike during field potential recording. This compound likewise depressed the amplitude of EPSPs observed with whole-cell recording. The 1S,3R isomer of t-ACPD was effective in depressing transmission, whereas the 1R,3S isomer was without effect at 50 microM. The cis isomer of ACPD (c-ACPD) also depressed transmission at concentrations from 25 to 100 microM. 3. Depression of population spike or EPSP amplitude by t-ACPD was not altered in the presence of the putative metabotropic receptor antagonist L-aminophosphonopropionic acid (AP3, 1 mM). In addition, the depressant action of t-ACPD on the population spike was not mimicked by aminophosphonobutyric acid, which has been shown to produce synaptic depression at other excitatory synapses.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, Tennessee 37232-0615.
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Lovinger
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Tyler
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Fidler
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Merritt
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology; D003342:Corpus Striatum / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D066298:In Vitro Techniques; D009474:Neurons / Q000502:physiology; D051381:Rats; D017470:Receptors, Glutamate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects
D017470:Receptors, Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D015761:4-Aminopyridine; D002118:Calcium