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)
Lovinger
D M
DM
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, Tennessee 37232-0615.
Tyler
E
E
Fidler
S
S
Merritt
A
A
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