本文選題：大鼠海馬 + 毒蕈堿型膽堿受體　； 參考：《中國(guó)科學(xué)技術(shù)大學(xué)》2008年博士論文

【摘要】： 膽堿能系統(tǒng)可以影響海馬突觸傳遞和突觸可塑性,從而在海馬的學(xué)習(xí)和記憶功能扮演著重要的角色。膽堿能調(diào)控作用主要通過(guò)毒蕈堿型膽堿受體(mAChR)。毒蕈堿型膽堿受體有M_1-M_5五種亞型,關(guān)于這五種亞型在膽堿的突觸傳遞和突觸可塑性調(diào)控中所起到的作用,目前仍不是十分清楚。鉛是環(huán)境中的一種重金屬污染物,具有神經(jīng)毒性。鉛暴露對(duì)多種遞質(zhì)系統(tǒng)以及神經(jīng)系統(tǒng)功能都造成損傷。對(duì)于膽堿能調(diào)控是否也包括在鉛的神經(jīng)毒理內(nèi)很少見(jiàn)報(bào)道。本文運(yùn)用電生理學(xué)實(shí)驗(yàn)方法,研究海馬中毒蕈堿型膽堿能系統(tǒng)對(duì)突觸傳遞和突觸可塑性的調(diào)控以及鉛對(duì)這種膽堿能調(diào)控的影響。 1.在海馬齒狀回區(qū)域(DG)內(nèi)注射各種毒蕈堿型膽堿受體配體,在位記錄興奮性突觸后電位,研究各種毒蕈堿型膽堿受體在突觸傳遞和可塑性調(diào)控中的作用。結(jié)果表明,一種非選擇性毒蕈堿型膽堿受體阻斷劑阿托品可以壓抑長(zhǎng)時(shí)程增強(qiáng)(LTP)的誘導(dǎo),證實(shí)了海馬內(nèi)毒蕈堿型膽堿系統(tǒng)參與了LTP的誘導(dǎo)。我們研究了M_(2/4)型膽堿受體拮抗劑和M_(3/5)AChR型膽堿受體拮抗劑對(duì)LTP的影響。發(fā)現(xiàn)向海馬內(nèi)注射M_1型膽堿受體拈抗劑和M_(2/4)型膽堿受體拮抗劑可以明顯壓抑LIP的誘導(dǎo),而M_(3/5)AChR型膽堿受體拮抗劑則對(duì)LTP沒(méi)有作用。結(jié)果表明毒蕈堿型膽堿能系統(tǒng)對(duì)突觸傳遞和突觸可塑性的調(diào)控是通過(guò)不同的受體亞型實(shí)現(xiàn)的。 2.應(yīng)用離體記錄技術(shù),研究了大鼠海馬雪氏側(cè)枝—CA1錐體神經(jīng)元突觸傳遞的毒蕈堿型膽堿能調(diào)控及鉛對(duì)這種調(diào)控的作用。carbachol是膽堿能受體的激動(dòng)劑。在本實(shí)驗(yàn)中,灌流5 M carbacbol使大鼠海馬CA1錐體神經(jīng)元的谷氨酸能EPSC幅度減小,這種抑制效應(yīng)主要是由M型乙酰膽堿受體介導(dǎo)的。在使用美加明(mecamylamine,10M)阻斷N型乙酰膽堿受體的作用后,carbacbol通過(guò)M型膽堿受體介導(dǎo)濃度依賴性地抑制EPSC;5M carbacbol增強(qiáng)了雙脈沖易化效應(yīng)和10Hz串刺激反應(yīng);并且降低了sEPSCs的頻率,減小了sEPSCs的幅度和衰減時(shí)間。在相同條件下,10M鉛離子灌流對(duì)于谷氨酸能EPSC的幅度沒(méi)有顯著性的影響,但是輕微地削弱了carbacbol對(duì)EPSC的壓抑作用;鉛抑制了carbachol對(duì)PPF和串刺激反應(yīng)的增強(qiáng)作用;10 M鉛降低了sEPSCs的頻率和衰減,并且阻斷了carbachol的進(jìn)一步作用;10 M鉛對(duì)sEPSCs的幅度沒(méi)有顯著性的作用,而且對(duì)carbachol的抑制作用也沒(méi)有顯著影響。膽堿能系統(tǒng)通過(guò)突觸前和突觸后的mAChRs對(duì)海馬的突觸傳遞和突觸可塑性的調(diào)控作用,對(duì)學(xué)習(xí)和記憶功能有重要的意義。鉛可能通過(guò)損傷谷氨酸能突觸傳遞的膽堿能調(diào)控作用來(lái)影響突觸傳遞效能和突觸可塑性,可能是鉛損傷學(xué)習(xí)記憶功能的機(jī)制之一。
[Abstract]:Cholinergic system plays an important role in learning and memory function of hippocampus by affecting synaptic transmission and synaptic plasticity. Cholinergic regulation is mainly mediated by muscarinic choline receptor mAChRN. Muscarinic choline receptors have five subtypes of M_1-M_5. The roles of these five subtypes in synaptic transmission and synaptic plasticity regulation of choline are still unclear. Lead is a heavy metal pollutant in the environment and has neurotoxicity. Lead exposure can damage many transmitter systems and nervous system functions. Whether cholinergic regulation is also included in the neurotoxicology of lead is rarely reported. The regulation of synaptic transmission and synaptic plasticity by muscarinic cholinergic system in the hippocampus and the effect of lead on the regulation of this cholinergic system were studied by electrophysiological experiments. 1. Various muscarinic choline receptor ligands were injected into the dentate gyrus of the sea horse. Excitatory postsynaptic potentials were recorded in situ to study the role of various muscarinic choline receptors in synaptic transmission and plasticity regulation. The results showed that atropine, a non-selective muscarinic choline receptor blocker, could inhibit the induction of long term potentiation of LTP, which confirmed that the muscarinic choline system in the hippocampus was involved in the induction of LTP. We studied the effects of M _ S _ 2 / 4) choline receptor antagonist and M_(3/5)AChR type choline receptor antagonist on LTP. It was found that intrahippocampal injection of type 1 choline receptor antagonist and Mass 2 / 4) choline receptor antagonist could significantly inhibit the induction of LIP, but M_(3/5)AChR type choline receptor antagonist had no effect on LTP. The results showed that muscarinic cholinergic system regulated synaptic transmission and synaptic plasticity through different receptor subtypes. 2. In vitro recording technique was used to study the muscarinic cholinergic regulation of synaptic transmission in rat hippocampal lateral branch CA1 pyramidal neurons and the effect of lead on this regulation. Carbachol is an agonist of cholinergic receptor. In this experiment, the glutamate EPSC amplitude of rat hippocampal CA1 pyramidal neurons was decreased by perfusion of 5 M carbacbol. This inhibitory effect was mainly mediated by M type acetylcholine receptor. After blocking N-type acetylcholine receptor (N-type acetylcholine receptor) with mecamylamine (10M), carbacbol inhibited EPSC-5M carbacbol in a concentration-dependent manner through M-type choline receptor mediated inhibition, enhanced the double-pulse facilitation effect and 10Hz cascade stimulation, and reduced the frequency of sEPSCs. The amplitude and attenuation time of sEPSCs are reduced. Under the same conditions, 10 M lead ion perfusion had no significant effect on the amplitude of glutamatergic EPSC, but slightly weakened the inhibitory effect of carbacbol on EPSC. Lead inhibited the effect of carbachol on the enhancement of PPF and cascade stimuli. 10 M lead decreased the frequency and attenuation of sEPSCs, and blocked the further effect of carbachol. 10 M lead had no significant effect on the amplitude of sEPSCs. Moreover, there was no significant effect on the inhibition of carbachol. Cholinergic system plays an important role in learning and memory by regulating synaptic transmission and synaptic plasticity through pre-synaptic and postsynaptic mAChRs. Lead may affect synaptic transmission efficiency and synaptic plasticity by damaging cholinergic regulation of glutaminergic synaptic transmission, which may be one of the mechanisms of lead damage of learning and memory function.
【學(xué)位授予單位】：中國(guó)科學(xué)技術(shù)大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2008
【分類號(hào)】：R338

【引證文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前1條

1 陳小剛;癲癇尖波對(duì)Theta節(jié)律動(dòng)態(tài)特性影響的研究[D];河北工業(yè)大學(xué);2011年

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本文編號(hào)：1906802