PROPERTIES OF A PRESYNAPTIC METABOTROPIC GLUTAMATE RECEPTOR IN RAT NEOSTRIATAL SLICES

1. The effect of the metabotropic glutamate receptor agonist trans-1-a minocyclopentane-1,3-dicarboxylic acid (t-ACPD) on glutamatergic trans mission at corticostriate synapses was examined using slices of neostr iatum. Field potential recordings were performed in slices from adult animals, and the effects of t-ACPD on the synaptically driven populati on 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 neuron al membrane properties were examined. In addition, the effects of puta tive metabotropic receptor agonists and antagonists and 4-aminopyridin e were examined. The ability of these compounds to mimic t-ACPD or blo ck its actions were determined. 2. Application of t-ACPD (5-100 muM) d epressed the maximal amplitude of the synaptically driven population s pike during field potential recording. This compound likewise depresse d the amplitude of EPSPs observed with whole-cell recording. The 1S,3R isomer of t-ACPD was effective in depressing transmission, whereas th e 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 mu M. 3. Depression of population spike or EPSP amplitude by t-ACPD was n ot altered in the presence of the putative metabotropic receptor antag onist L-aminophosphonopropionic acid (AP3, 1 mM). In addition, the dep ressant action oft-ACPD on the population spike was not mimicked by am inophosphonobutyric acid, which has been shown to produce synaptic dep ression at other excitatory synapses. 4. The depressant action of t-AC PD was reduced by low concentrations of the K+ channel antagonist 4-am inopyridine (4-AP, 30 muM) when recordings were performed in artificia l 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 presen t study extends our earlier observations indicating that t-ACPD activa tes a presynaptic receptor that depresses glutamate release at cortico striate synapses. Importantly, we have demonstrated that t-ACPD depres ses 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-i nsensitive receptor. 7. This receptor appears to reduce glutamate rele ase via a 4-AP-sensitive mechanism similar to that employed by other p resynaptic receptors.