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大鼠海马神经元对于高频脉冲刺激的暂态响应
引用本文:胡一凡,封洲燕,王兆祥,郑吕漂.大鼠海马神经元对于高频脉冲刺激的暂态响应[J].生物化学与生物物理进展,2021,48(7):827-835.
作者姓名:胡一凡  封洲燕  王兆祥  郑吕漂
作者单位:浙江大学生物医学工程与仪器科学学院,生物医学工程教育部重点实验室,杭州 310027,浙江大学生物医学工程与仪器科学学院,生物医学工程教育部重点实验室,杭州 310027,浙江大学生物医学工程与仪器科学学院,生物医学工程教育部重点实验室,杭州 310027,浙江大学生物医学工程与仪器科学学院,生物医学工程教育部重点实验室,杭州 310027
基金项目:国家自然科学基金(30970753)资助项目.
摘    要:闭环刺激是深部脑刺激(deep brain stimulation,DBS)的重要发展方向之一,有望用于治疗多种脑神经系统疾病.与常规开环的长时间持续刺激不同,闭环刺激通常采用短促的高频脉冲序列.而神经元对于高频刺激的响应存在暂态过程,在初期的短时间内会发生很大变化,从而影响闭环刺激的作用.为了研究这种暂态过程,在大鼠海马CA1区传出轴突纤维(alveus)上施加不同频率的恒频以及随机变频的逆向高频刺激(antidromic high-frequency stimulation,A-HFS),并以逆向诱发的群峰电位(antidromically-evoked population spike,APS)的幅值作为指标来考察神经元群体的响应.研究结果表明,100、133和200 Hz的恒频A-HFS初期,APS迅速衰减,脉冲频率越高,APS衰减越快.平均不到1 s时间内APS的幅值就会下降一半以上,100 Hz时的平均半衰期为~0.96 s,频率增加1倍至200 Hz时,平均半衰期缩短至~0.21 s.使用100~200 Hz范围内实时微调脉冲间隔的随机变频刺激,则可以显著延缓神经元响应的衰减速度,延长刺激作用的维持时间.这些结果可以为短促闭环刺激等DBS新模式的开发提供依据.

关 键 词:高频刺激  暂态响应  群峰电位  脉冲频率  脉冲间隔
收稿时间:2020/9/8 0:00:00
修稿时间:2020/11/13 0:00:00

Transient Neuronal Responses to High-frequency Pulse Stimulation in Rat Hippocampus
Institution:Key Laboratory of Biomedical Engineering of Education Ministry, College of Biomedical Engineering and Instrumentation Science, Zhejiang University, Hangzhou 310027, China,Key Laboratory of Biomedical Engineering of Education Ministry, College of Biomedical Engineering and Instrumentation Science, Zhejiang University, Hangzhou 310027, China,Key Laboratory of Biomedical Engineering of Education Ministry, College of Biomedical Engineering and Instrumentation Science, Zhejiang University, Hangzhou 310027, China,Key Laboratory of Biomedical Engineering of Education Ministry, College of Biomedical Engineering and Instrumentation Science, Zhejiang University, Hangzhou 310027, China
Abstract:Closed-loop stimulation is one of the important development directions of deep brain stimulation (DBS) that is promising for treating various brain disorders. Contrast to the conventional open-loop stimulation with continuous stimulation for long periods of time, the closed-loop stimulation usually utilizes short sequences of high-frequency pulses. However, neuronal responses to the high-frequency stimuli may change substantially in a short period of time because of the transient process at the beginning of stimulation. The change may affect the stimulation efficacy. To investigate the transient process of high-frequency stimuli, antidromic high-frequency stimulation (A-HFS) with different constant pulse frequencies as well as varying frequency was applied at the alveus of rat hippocampal CA1 region. The amplitude of antidromically-evoked population spike (APS) was used as an index to evaluate the neuronal responses to A-HFS. The results show that at the initial period of A-HFS with a constant pulse frequency of 100, 133 and 200 Hz, the APS decreased rapidly. A higher pulse frequency generated a faster attenuation of the APS. The mean amplitudes of APS decreased by more than half within less than 1 s. The mean half-value time of APS amplitude was ~0.96 s with 100 Hz A-HFS and decreased to ~0.21 s with the pulse frequency doubled to 200 Hz. With randomly-varying frequencies in the range of 100-200 Hz to tune the pulse interval in real time, the attenuation speed of neuronal responses was significantly slowed down to prolong the maintenance of the stimulation effect. These results provide clues to develop new DBS paradigms for the implementation of short closed-loop stimulations.
Keywords:high-frequency stimulation  transient response  population spike  pulse frequency  inter-pulse interval
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