Analysing metabotropic glutamate group III receptor mediated modulation ofsynaptic transmission in the amygdala-kindled dentate gyrus of the rat

Metabotropic glutamate receptors (mGluRs) provide a powerful control of syn aptic transmission in the hippocampus and may serve as a target for drug de velopment in human temporal lobe epilepsies. Agonists and antagonists at th ese receptors influence the development and propagation of seizures in some animal models of epilepsy. Experimental seizures can change the level of e xpression of mGluRs in the rat hippocampus. In the human dentate gyrus of p atients suffering from temporal lobe epilepsy (TLE), group III mGluR mediat ed inhibition of synaptic transmission is almost lost in the sub-group with Ammon's horn sclerosis. We tested the modulation of synaptic transmission by the group III mGluR specific agonist L(+)-2-amino-4-phosphonobutyric aci d (L-AP4) in the dentate gyrus outer molecular layer in control and amygdal a-kindled rats, a common model for TLE. Extracellular field potential recor dings upon subthreshold stimulation of lateral perforant path fibers were m easured simultaneously in the outer molecular layer and granule cell layer. Analysis of 'paired-pulse' characteristics in the absence and presence of L-AP4 and group III mGluR mediated inhibition of synaptic transmission in t he lateral perforant path revealed no significant alterations in fully kind led rats. Since there is no evidence of altered L-AP4 responses, a loss of group III mGluR function, particularly that of subtype mGluR8, seems not ne cessary for the kindling epilepsy. (C) 1999 Elsevier Science B.V. All right s reserved.