- 作者: Po-Wu Gean; Fang-Chia Chang; Pei-Lu Yi; Jju-Home Lin; Jing-Jane Tsai
- 作者服務機構: Department of; a Pharmacology and; b Neurology, College of Medicine, National; Cheng-Kung University, Tainan, Taiwan, Republic of China
- 中文摘要: --
- 英文摘要: The mechanism responsible for long-term depression (LTD) of pharmacologi- cally 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 (50μ M), 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 EPSPNM- DA. However, coupling postsynaptic depolarization with synaptic activity induced LTD. The EPSPNMDA LTD could be blocked by L-2-amino-3-phos- phonopropionic acid (50 μM) or (RS)-α-methyl-4-carboxyphenylglycine (200 μM), specific antagonists for metabotropic glutamate receptors (mG1uR). Furthermore, application of trans-l-aminocyclopentane-l,3-dicar- boxylic acid (t-ACPD, 50μM), a specific mG1uR agonist, in conjunction with postsynaptic depolarizing elicited LTD. In contrast, the mG1uR agonists quis- qualate or t-ACPD when given alone produced a sustained enhancement of EPSPNMDA. Finally, coupled depolarization did not evoke LTD in slices pre- treated with the protein kinase C (PKC) inhibitor calphostin c (60 nM). The present results demonstrate that activation of mG1uR is necessary for the induction of LTD of EPSPNMDA and suggest that NMDA receptors are subject to bidirectional regulation by mG1uR. Furthermore, the induction of LTD is likely to involve the stimulation of PKC.
- 中文關鍵字: --
- 英文關鍵字: Glutamate receptor; Long-term depression; N-Methyl-D-aspartate; Hippocampus