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毒蕈碱型胆碱能系统对海马突触传递和可塑性的调控及铅的作用

发布时间:2018-05-18 18:56

  本文选题:大鼠海马 + 毒蕈碱型胆碱受体 ; 参考:《中国科学技术大学》2008年博士论文


【摘要】: 胆碱能系统可以影响海马突触传递和突触可塑性,从而在海马的学习和记忆功能扮演着重要的角色。胆碱能调控作用主要通过毒蕈碱型胆碱受体(mAChR)。毒蕈碱型胆碱受体有M_1-M_5五种亚型,关于这五种亚型在胆碱的突触传递和突触可塑性调控中所起到的作用,目前仍不是十分清楚。铅是环境中的一种重金属污染物,具有神经毒性。铅暴露对多种递质系统以及神经系统功能都造成损伤。对于胆碱能调控是否也包括在铅的神经毒理内很少见报道。本文运用电生理学实验方法,研究海马中毒蕈碱型胆碱能系统对突触传递和突触可塑性的调控以及铅对这种胆碱能调控的影响。 1.在海马齿状回区域(DG)内注射各种毒蕈碱型胆碱受体配体,在位记录兴奋性突触后电位,研究各种毒蕈碱型胆碱受体在突触传递和可塑性调控中的作用。结果表明,一种非选择性毒蕈碱型胆碱受体阻断剂阿托品可以压抑长时程增强(LTP)的诱导,证实了海马内毒蕈碱型胆碱系统参与了LTP的诱导。我们研究了M_(2/4)型胆碱受体拮抗剂和M_(3/5)AChR型胆碱受体拮抗剂对LTP的影响。发现向海马内注射M_1型胆碱受体拈抗剂和M_(2/4)型胆碱受体拮抗剂可以明显压抑LIP的诱导,而M_(3/5)AChR型胆碱受体拮抗剂则对LTP没有作用。结果表明毒蕈碱型胆碱能系统对突触传递和突触可塑性的调控是通过不同的受体亚型实现的。 2.应用离体记录技术,研究了大鼠海马雪氏侧枝—CA1锥体神经元突触传递的毒蕈碱型胆碱能调控及铅对这种调控的作用。carbachol是胆碱能受体的激动剂。在本实验中,灌流5 M carbacbol使大鼠海马CA1锥体神经元的谷氨酸能EPSC幅度减小,这种抑制效应主要是由M型乙酰胆碱受体介导的。在使用美加明(mecamylamine,10M)阻断N型乙酰胆碱受体的作用后,carbacbol通过M型胆碱受体介导浓度依赖性地抑制EPSC;5M carbacbol增强了双脉冲易化效应和10Hz串刺激反应;并且降低了sEPSCs的频率,减小了sEPSCs的幅度和衰减时间。在相同条件下,10M铅离子灌流对于谷氨酸能EPSC的幅度没有显著性的影响,但是轻微地削弱了carbacbol对EPSC的压抑作用;铅抑制了carbachol对PPF和串刺激反应的增强作用;10 M铅降低了sEPSCs的频率和衰减,并且阻断了carbachol的进一步作用;10 M铅对sEPSCs的幅度没有显著性的作用,而且对carbachol的抑制作用也没有显著影响。胆碱能系统通过突触前和突触后的mAChRs对海马的突触传递和突触可塑性的调控作用,对学习和记忆功能有重要的意义。铅可能通过损伤谷氨酸能突触传递的胆碱能调控作用来影响突触传递效能和突触可塑性,可能是铅损伤学习记忆功能的机制之一。
[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.
【学位授予单位】:中国科学技术大学
【学位级别】:博士
【学位授予年份】:2008
【分类号】:R338

【引证文献】

相关硕士学位论文 前1条

1 陈小刚;癫痫尖波对Theta节律动态特性影响的研究[D];河北工业大学;2011年



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