LONG-LASTING ENHANCEMENT OF NMDA RECEPTOR-MEDIATED SYNAPTIC TRANSMISSION BY METABOTROPIC GLUTAMATE-RECEPTOR ACTIVATION

SYNAPTIC transmission mediated by the N-methyl-D-aspartate (NMDA) glut amate receptor plays a key role in a range of plastic processes in the nervous system. These include long-term potentiation of synaptic tran smission mediated by the pha-amino-3-hydroxy-5-methyl-4-isoxazolepropi onate (AMPA) receptor, neuronal development, excitotoxicity and certai n learning tasks1,2. Recently, long-term potentiation of NMDA receptor -mediated synaptic transmission was found to occur following high-freq uency (tetanic) stimulation via an unknown mechanism3-7. We show here that activation of metabotropic glutamate (mGlu) receptors by neurally released transmitter underlies this type of long-term potentiation. T he whole-cell patch-clamp technique in the 'thick' slice of the rat de ntate gyrus was used to measure NMDA receptor-mediated excitatory post synaptic currents. We have found that mGlu receptor activation by a se lective agonist produced a long-lasting enhancement which was mutually exclusive with long-term potentiation of these NMDA currents. Moreove r, both forms of potentiation were greatly reduced by the mGlu recepto r antagonists L-2-amino-3-phosphonopropionate and (R,S)-alpha-methyl-4 -carboxyphenylglycine.