Hashimoto Ayumi, Sawada Toyohiro, Natsume Kiyohisa
Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu, Fukuoka 808-0196, Japan.
Biophys Physicobiol. 2017 Sep 5;14:137-146. doi: 10.2142/biophysico.14.0_137. eCollection 2017.
The study aimed to determine whether and how the activation of the acetylcholine receptor affects epileptiform discharges in the CA3 region in a rat hippocampus. Picrotoxin (100 μM), a GABA receptor antagonist, was applied to a hippocampal slice to induce epileptiform discharges. The effects of the cholinergic agonist, carbachol, on the discharges were examined at the several concentrations (1-30 μM). Carbachol had different impacts on epileptiform discharges at the different concentrations. Relatively low concentrations of carbachol (<10 μM) increased the frequency but decreased the amplitude of the discharges. At 10 μM, carbachol induced the discharges, including bursts of theta frequency oscillations. At 30 μM, carbachol could induce bursts of beta frequency oscillations instead of epileptiform discharges. The amplitudes of the oscillations were smaller than those of the discharges. Carbachol suppressed the evoked population EPSPs (pEPSPs) in a dose-dependent manner. These effects were blocked by the muscarinic cholinergic receptor antagonist atropine sulfate. The high level of muscarinic receptor activation can replace epileptiform discharges with theta or beta oscillation. These results suggest that the dose-dependent alternation of the acetylcholine receptor activation may provide the three different stages the epileptiform discharges, the bursts of theta oscillation, and the bursts of the beta oscillation.
该研究旨在确定乙酰胆碱受体的激活是否以及如何影响大鼠海马体CA3区的癫痫样放电。将GABA受体拮抗剂印防己毒素（100 μM）应用于海马切片以诱导癫痫样放电。在几种浓度（1-30 μM）下检测了胆碱能激动剂卡巴胆碱对放电的影响。卡巴胆碱在不同浓度下对癫痫样放电有不同影响。相对低浓度的卡巴胆碱（<10 μM）增加了放电频率但降低了放电幅度。在10 μM时，卡巴胆碱诱导放电，包括θ频率振荡的爆发。在30 μM时，卡巴胆碱可诱导β频率振荡的爆发而非癫痫样放电。振荡的幅度小于放电的幅度。卡巴胆碱以剂量依赖性方式抑制诱发的群体兴奋性突触后电位（pEPSPs）。这些作用被毒蕈碱胆碱能受体拮抗剂硫酸阿托品阻断。高水平的毒蕈碱受体激活可以用θ或β振荡替代癫痫样放电。这些结果表明，乙酰胆碱受体激活的剂量依赖性改变可能提供癫痫样放电、θ振荡爆发和β振荡爆发这三个不同阶段。
