THE INVOLVEMENT OF METABOTROPIC GLUTAMATE RECEPTORS IN LONG-TERM DEPRESSION OF N-METHYL-D-ASPARTATE RECEPTOR-MEDIATED SYNAPTIC POTENTIAL INTHE RAT HIPPOCAMPUS

The frequency-dependent long-term modifications of pharmacologically i solated N-methyl-D-aspartate (NMDA) receptor-mediated excitatory posts ynaptic potential (EPSP(NMDA)) was studied. Intracellular recordings w ere obtained from CA1 cells of rat hippocampal slices and in the prese nce of 6-cyano-7-nitroquinoxaline-2,3-dione (10 mu M) and bicuculline (20 mu M) which block non NMDA and GABA(A) receptors, respectively. Lo w-frequency stimulation at 5 Hz resulted in a long-term depression (LT D) of EPSP(NMDA) in 12 of 17 cells. However, when the stimulus frequen cy was increased to 30 Hz, a long-term potentiation (LTP) of EPSP(NMDA ) was observed in 7 out of 9 cells. The LTD was not affected by pretre ating the slices with okadaic acid (0.5-1 mu M) suggesting that activa tion of endogenous protein phosphatase is not responsible for this pro cess. In the presence of L-2-amino-3-phosphonopropionic acid (50 mu M) or (RS)-alpha-methyl-4-carboxyphenylglycine (200 mu M), 5 Hz tetaniza tion resulted in LTP instead of LTD. These results suggest that activa tion of metabotropic glutamate receptor (mGluR) is necessary for the i nduction of EPSP(NMDA) LTD and blockade of mGluR unmasks a LTP.