权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The role of GABAAreceptors and inhibitory neuron network on anesthetic-induced neural inhibition

GABAA 受体和抑制神经元网络在麻醉诱导的神经抑制中的作用

基本信息

批准号：
17390425
负责人：
NISHIKAWA Koichi
金额：
$ 7.84万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

项目摘要

Background: The cellular mechanisms of anesthetic-induced amnesia are still poorly understood. The present study examined the effects of sevoflurane at various concentrations on excitatory synaptic transmission and on long-term potentiation (LTP) as a possible mechanism contributing to loss of recall in the CA1 region of rat hippocampal slices. Methods: Population spikes (PS) and field excitatory postsynaptic potentials (fEPSPs) were recorded using extracellular electrodes following electrical stimulation of Schaffer-collateral-commissural (SCC) fiber inputs. Paired pulse facilitation (PPF) was used as a measure of presynaptic effects of the anesthetic LTP was induced using tetanic stimulation (100 Hz, 1 s) of the SCC pathway. Sevoflurane at subanesthetic (0.5%) to anesthetic concentrations (28-5.0%) was applied to slices in artificial cerebrospinal fluid solution.Results: In the presence of subanesthetic sevoflurane (0.5%), PS amplitude was significantly depressed and tetanic stimulation induced only post-tetanic potentiation (PTP) and then failure of LTP. These inhibitory effects were antagonized by bicuculline (10μM), a GABA_A receptor antagonist. In addition, anesthetic sevoflurane further depressed fEPSP amplitude in a dose-dependent manner, and completely blocked LTP. Bicuculline only partially antagonized anesthetic sevoflurane-induced profound inhibition of LTP. Anesthetic but not subanesthetic, sevoflurane significantly increased PPF, suggesting that anesthetic sevoflurane has presynaptic actions to reduce glutamate release from nerve terminals.Conclusions: The present study provides evidence that subanesthetic sevoflurane inhibits long-term potentiation of hippocampal CA1 neurons through GABAergic mechanisms, and these actions alone seem to account for the effects of subanesthetic sevoflurane on synaptic plasticity.

背景：麻醉诱导的遗忘的细胞机制仍然知之甚少。本研究探讨了不同浓度的七氟烷对兴奋性突触传递和长时程增强（LTP）的影响，这可能是导致大鼠海马脑片CA1区回忆丧失的机制。研究方法：群体尖峰（PS）和场兴奋性突触后电位（fEPSP）记录使用细胞外电极后，电刺激谢弗侧支连合（SCC）纤维输入。成对脉冲易化（PPF）被用作麻醉剂的突触前效应的测量，LTP使用SCC通路的强直刺激（100 Hz，1 s）诱导。结果：0.5%七氟醚使PS振幅显著降低，强直刺激仅引起强直后增强（PTP），随后LTP消失。GABA_A受体拮抗剂荷包牡丹碱（10μM）可拮抗这种抑制作用。此外，麻醉剂七氟烷以剂量依赖性方式进一步降低fEPSP振幅，并完全阻断LTP。荷包牡丹碱仅部分拮抗麻醉剂七氟醚诱导的LTP的深度抑制。麻醉，但不是亚麻醉，七氟烷显着增加PPF，表明麻醉七氟烷有突触前行动，以减少谷氨酸释放从nerve terminals.Conclusions：本研究提供的证据表明，亚麻醉七氟烷抑制长时程增强海马CA1区神经元通过GABA能机制，这些行动似乎占亚麻醉七氟烷对突触可塑性的影响。