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在老鼠海馬迴CA1的錐狀細胞給一個高頻率的連續刺激,會誘使細胞產生"
長期增益現象",即LTP.LTP是研究哺乳類動物學習和記憶的一種模式.而
LT P能否產生,與突觸後NMDA受體是否被活化,兩者之間有非常密切的關
係.因此我們利用藥理學的方法,給予non-NMDA受體拮抗劑:CNQX 10
mircoM 和 GABA-A受體拮抗劑:BMI 20 microM 就能分離得到一經由NMDA
受體所產生的突觸電位,稱之為EPSP-NMDA.我們發現在EPSP-NMDA的情況
下,給細胞一低頻率的連續刺激(ex:5Hz)會產生"長期抑制現象",即LTD.隨
著刺激頻率的提高(ex:30Hz,100Hz),會誘導細胞產生LTP.因此要細胞產生
LTP或LTD,依賴所給予的刺激頻率大小,即具有"頻率相關性"之特性.而此
LTD的現象不會被protein phosphatase的抑制劑:okadaic acid所抑制,但
此現象卻可被 metabotropic 受體的拮抗劑:AP3 或 MCPG 所阻斷.我們進
一步發現給予 protein kinase C (PKC) 的抑制劑:calphostin c 同樣能
抑制LTD的產生 .因此我們認為此LTD的機轉是藉由metabotropic受體活
化 G-蛋白,使得 phospholipase C (PLC)活化,造成phosphoinositol
hydrolysis,進而產生了PKC才導致了LTD.
A brief repetitive stimulation applied to afferent fibers
ending on CA1 pyramidal neurons produces the form of synaptic
plastici- ty known as long-term potentiation (LTP),which is
widely studied as a model for learing and memory.Activation of
NMDA receptors is critically important in the induction of LTP.
Thus,modulating the activity of this receptor may be an
effective means of regu- lating learning and memory .In this
study,we isolated the NMDA receptor-mediated synaptic potential
(EPSP-NMDA) pharmacologic- ally in the hippocampus CA1 neurons
by application of a solution containing CNQX (10 microM) and
picrotoxin (50 microM) (or bicu- culline 20 microM) that block
non-NMDA and GABA-A receptors res- pectively.We found that
tetanic stimulation of the afferent fi- bers can induce either
LTP or long-term depression (LTD) depend- ing on the
stimulation frequencies.High-frequency stimulation ( 100 Hz)
resulted in the LTP of EPSP-NMDA.With moderate-frequency
stimulation (10 Hz),six neurons showed LTD and five showed LTP.
LTD is obtained when low-frequency stimulation (5 Hz) is used.
This synaptic depression can be reversed by the pretreatment of
slices with AP3 (50 microM) or MCPG (200 microM) suggesting the
involvement of metabotropic glutamate receptors.Therefore, the
long-term modification of NMDA receptor-mediated synaptic
poten- tial is dependent on the frequency of stimulation.
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