The involvement of metabotropic glutamate receptors in long-term depression of N-methyl-D-aspartate receptor-mediated synaptic potential in the rat hippocampus.
The frequency-dependent long-term modifications of pharmacologically isolated N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic potential (EPSPNMDA) was studied. Intracellular recordings were obtained from CA1 cells of rat hippocampal slices and in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM) and bicuculline (20 microM) which block non-NMDA and GABAA receptors, respectively. Low-frequency stimulation at 5 Hz resulted in a long-term depression (LTD) of EPSPNMDA in 12 of 17 cells. However, when the stimulus frequency was increased to 30 Hz, a long-term potentiation (LTP) of EPSPNMDA was observed in 7 out of 9 cells. The LTD was not affected by pretreating the slices with okadaic acid (0.5-1 microM) suggesting that activation of endogenous protein phosphatase is not responsible for this process. In the presence of L-2-amino-3-phosphonopropionic acid (50 microM) or (RS)-alpha-methyl-4-carboxyphenylglycine (200 microM), 5 Hz tetanization resulted in LTP instead of LTD. These results suggest that activation of metabotropic glutamate receptor (mGluR) is necessary for the induction of EPSPNMDA LTD and blockade of mGluR unmasks a LTP.
Yi
P L
PL
Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan City, Taiwan, Republic of China.
Chang
F C
FC
Tsai
J J
JJ
Hung
C R
CR
Gean
P W
PW
D000818:Animals; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate; D009435:Synaptic Transmission / Q000502:physiology*
D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid