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 muM) 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 muM. The cis isomer of ACPD (c-ACPD) also depressed transmission at concentrations from 25 to 100 muM. 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 oft-ACPD on the population spike was not mimicked by aminophosphonobutyric acid, which has been shown to produce synaptic depression at other excitatory synapses. 4. The depressant action of t-ACPD was reduced by low concentrations of the K+ channel antagonist 4-aminopyridine (4-AP, 30 muM) when recordings were performed in artificial cerebrospinal fluid containing 2 mM [Ca2+]o. The synaptic depressant action of c-ACPD was also reduced in the presence of 4-AP. Reduction of [Ca2+]o to 0.3 mM reversed the effect of 4-AP, as evidenced by the return of synaptic depression in the presence of t-ACPD. 5. The present study extends our earlier observations indicating that t-ACPD activates a presynaptic receptor that depresses glutamate release at corticostriate synapses. Importantly, we have demonstrated that t-ACPD depresses synaptic transmission in adult animals as well as in younger rats. 6. The profile of action of agonists is consistent with activation of a metabotropic glutamate receptor. However, it appears to be an AP3-insensitive receptor. 7. This receptor appears to reduce glutamate release via a 4-AP-sensitive mechanism similar to that employed by other presynaptic receptors.
