ANTAGONISM OF MGLU RECEPTORS AND POTENTIATION OF EPSCS AT RAT SPINAL MOTONEURONS IN-VITRO

The patch-clamp technique has been used to record synaptic responses, elicited by electrical stimulation of dorsal roots, in 28 single moton eurones of in vitro spinal cord preparations from neonate (P5 to P8) r ats. The effects of (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG) (200 mu M), a potent antagonist at L-2-amino-4-phosphonobutanoate (AP4 )-sensitive receptors, and (RS)-alpha-methyl-4-carboxyphenylglycine (M CPG) (500 mu M), which is a less selective antagonist of mGluRs, were tested on EPSCs alone and as antagonists of AP4-induced depression of EPSCs. The EC50 for depression of EPSCs by AP4 (1.16 +/- 0.12 mu M, n = 8) was increased to 18.9 +/- 0.7 mu M (n = 6) by MPPG. MCPG (500 mu M) had no significant effect on the depressant potency of AP4. Under c ontrol conditions, EPSCs had mean peak amplitudes of 983 pA +/- 64 SEM and mean charge transferred of 306 +/- 37 pC (n = 28). These values w ere increased significantly (p < 0.05) to 1168 +/- 68 pA and 363 +/- 3 9 pC by MPPG (n = 6), and 1150 +/- 54 pA and 358 +/- 33 pC (n = 6) by MCPG. There was no significant difference between the enhancement of t he initial peak of the EPSCs (mean latency from stimulus artifact 5.9 +/- 0.3 ms) and later components, suggesting mGluRs to be present on p rimary afferent terminals presynaptic to motoneurones as well as in pa thways via interneurones. These results are consistent with the presen ce of at least two types of presynaptic mGluR that modulate release of glutamate in segmental pathways convergent onto motoneurones. These r eceptors appear to be activated by interstitial glutamate tonically pr esent in the present preparations. (C) 1997 Elsevier Science Ltd.