Activation of metabotropic glutamate receptors in conjunction with postsynaptic depolarization triggers a long-term depression of the N-methyl-D-aspartate receptor-mediated synaptic potential in the rat hippocampus

Po-Wu Gean, Fang Chia Chang, Pei Lu Yi, Jju Home Lin, Jing Jane Tsai

研究成果: Article

摘要

The mechanism responsible for long-term depression (LTD) of pharmacologically isolated N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic potential (EPSPNMDA) was studied. Intracellular recordings were made from CA1 cells of rat hippocampal slices in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (10 μM) and picrotoxin (50 μM), which block non-NMDA and GABAA receptors, respectively. Intracellular injections of depolarizing pulses (500 ms, 0.3-0.7 nA) at 1 Hz for 5 min in the absence of synaptic stimulation caused a persistent increase in the amplitude of EPSPNMDA. However, coupling postsynaptic depolarization with synaptic activity induced LTD. The EPSPNMDA LTD could be blocked by L-2-amino-3-phosphonopropionic acid (50 μM) or (RS)-α-methyl-4-carboxyphenylglycine (200 μM), specific antagonists for metabotropic glutamate receptors (mGluR). Furthermore, application of trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD, 50 μM), a specific mGluR agonist, in conjunction with postsynaptic depolarizing elicited LTD. In contrast, the mGluR agonists quisqualate or t-ACPD when given alone produced a sustained enhancement of EPSPNMDA. Finally, coupled depolarization did not evoke LTD in slices pretreated with the protein kinase C (PKC) inhibitor calphostin c (60 n M). The present results demonstrate that activation of mGluR is necessary for the induction of LTD of EPSPNMDA and suggest that NMDA receptors are subject to bidirectional regulation by mGluR. Furthermore, the induction of LTD is likely to involve the stimulation of PKC.

原文English
頁(從 - 到)166-173
頁數8
期刊Journal of biomedical science
2
發行號2
DOIs
出版狀態Published - 1995 四月 1

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

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