METABOTROPIC GLUTAMATE RECEPTORS INHIBITING EXCITATORY SYNAPSES IN THE CA1 AREA OF RAT HIPPOCAMPUS

In the CA1 region of hippocampal slices prepared from young adult rats , we studied the ability of several specific agonists of metabotropic glutamate receptors (mGluRs) to depress excitatory synaptic transmissi on at the CAS-CAI pyramidal cell synapses. Three groups of mGluRs have been described: group 1 (mGluR1 and 5) receptors are positively coupl ed to phospholipase C whereas group 2 (mGluR2 and 3) and group 3 (mGlu R4, 6, 7 and 8) receptors are negatively coupled to adenylate cyclase. We found that the broad-spectrum agonist (1S,3R)-1-aminocyclopentyl-1 ,3-dicarboxylate and the group 1-specific agonist (R,S)-dihydroxypheny lglycine both reversibly inhibited evoked field excitatory postsynapti c potentials, indicating the involvement of group 1 mGluRs. (R,S)-3,5- dihydroxyphenylglycine presumably inhibited transmission via a presyna ptic mechanism, as whole-cell voltage-clamp recordings revealed that i nhibition of the synaptic transmission was always accompanied with an increase in paired-pulse facilitation. Treatment with a specific block er of mGluR1 receptors, the phenylglycine derivative (S)-4-carboxyphen ylglycine, was without effect on the ,3R)-1-amino-cyclopentyl-1,3-dica rboxylate-induced depression of the field excitatory postsynaptic pote ntials, strongly suggesting that mGluR5 receptors are responsible for the (1S,3R)-1-aminocydopentyl-1,3-dicarboxylate effect, Two selective agonists of group 2 mGluRs, (2S,1's,2's)-2-(2'-carboxycyclopropyl)glyc line and 4-carboxy-3-hydroxyphenylglycine, were totally ineffective in blocking CA3-CA1-evoked synaptic transmission, excluding the involvem ent of mGluR2/3 subtypes at this developmental stage.