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

背景：麻醉诱导健忘症的细胞机制尚不清楚。本研究探讨了不同浓度的七氟醚对兴奋性突触传递和长期增强（LTP）的影响，作为导致大鼠海马CA1区回忆丧失的可能机制。方法：采用细胞外电极记录schaffer - lateral-commissural （SCC）纤维输入电刺激后的群体峰（PS）和场兴奋性突触后电位（fEPSPs）。配对脉冲促进（PPF）被用来衡量使用破伤风刺激（100 Hz, 1 s） SCC通路诱导LTP的麻醉突触前效应。将亚麻醉浓度（0.5%）至麻醉浓度（28-5.0%）的七氟醚应用于人工脑脊液溶液中的切片。结果：在亚麻醉七氟醚（0.5%）的作用下，大鼠PS振幅明显下降，破伤风刺激仅引起破伤风后增强（PTP），随后LTP失效。这些抑制作用可被GABA_A受体拮抗剂双球茎碱（10μM）拮抗。此外，麻醉剂七氟醚以剂量依赖的方式进一步抑制fEPSP振幅，并完全阻断LTP。双库兰仅部分拮抗麻醉剂，七氟醚诱导的LTP深度抑制。麻醉而非亚麻醉，七氟醚显著增加PPF，提示麻醉七氟醚具有突触前作用，减少神经末梢的谷氨酸释放。结论：本研究提供的证据表明，亚麻醉七氟醚通过gaba能机制抑制海马CA1神经元的长期增强，这些作用似乎单独解释了亚麻醉七氟醚对突触可塑性的影响。

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.