海马区锥体神经元轴突高频电刺激对胞体的影响

Effects on Somata by High-frequency Electrical Stimulation at The Axons of Hippocampal Pyramidal Neurons

目的深部脑刺激(deep brain stimulation,DBS)利用持续的电脉冲高频刺激(high-frequency stimulation,HFS)调控神经元的活动,可望用于治疗更多脑疾病。为了深入了解HFS的作用机制,促进DBS的发展,本文研究轴突HFS在引起轴突阻滞期间神经元胞体的改变。方法在麻醉大鼠海马CA1区的锥体神经元轴突上施加脉冲频率为100 Hz的1 min逆向高频刺激(antidromic high-frequency stimulation,A-HFS)。为了研究胞体的响应,利用线性垂直排列的多通道微电极阵列,记录刺激位点上游CA1区锥体神经元胞体附近各结构分层上的诱发电位,包括A-HFS脉冲诱发的逆向群峰电位(antidromic population spike,APS)以及A-HFS期间施加的顺向测试脉冲诱发的顺向群峰电位(orthodromic population spike,OPS),并计算诱发电位的电流源密度(current-source density,CSD),用于分析A-HFS期间锥体神经元胞体附近动作电位的生成和传导。结果锥体神经元轴突上的A-HFS会减小胞体对于逆向和顺向兴奋的传导速度。并且,这种胞体变化的发生和恢复都比A-HFS诱导的轴突阻滞要缓慢。结论轴突上的持续高频刺激可以引起胞体产生变化,这种变化可能是胞体附近细胞膜电位改变所致。此发现有助于深入揭示脑神经系统电刺激的作用机制。

Objective Deep brain stimulation(DBS)utilizes sustained high-frequency stimulation(HFS)of electrical pulses to modulate neuronal activity.The therapy is expected to be used to treat more brain disorders.To deeply understand the mechanisms of the HFS to advance the DBS development,the present study investigates the effect of axonal HFS on neuronal somata during HFS-induced axonal block.Methods Antidromic highfrequency stimulation(A-HFS)with a 100-Hz pulse frequency and a 1-min duration was applied at the axons of pyramidal neurons in the hippocampal CA1 region of anesthetized rats.To investigate the responses of somata,a multi-channel microelectrode array with a vertical linear configuration was implanted to record the evoked potentials in the lamellas around the somata of CA1 pyramidal neurons at the upstream area of stimulation site,including the antidromic population spikes(APS)evoked by the pulses of A-HFS as well as the orthodromic population spikes(OPS)evoked by orthodromic test pulses applied during the A-HFS.Current-source densities(CSD)of the evoked potentials were calculated to evaluate the generation and propagation of action potentials around the somata of pyramidal neurons during A-HFS.Results A-HFS on the axons of pyramidal neurons slowed down the propagation speed of both antidromic and orthodromic excitations around somata.In addition,the occurrence and recovery of the changes of somata were slower than the A-HFS-induced axonal block.Conclusion Axonal HFS can induce soma alterations that might be caused by changes in membrane potentials nearby somata.The finding is helpful for deeply revealing the mechanisms of electrical stimulations of brain nervous system.