Ye Xiangyu, Feng Zhouyan, Wang Zhaoxiang, Zheng Lvpiao, Yuan Yue, Hu Yifan, Xu Yipeng
Key Laboratory for Biomedical Engineering of Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou 310027, China.
Research Center for Human-Machine Augmented Intelligence, Research Institute of Artificial Intelligence, Zhejiang Lab, Hangzhou 311121, China.
Brain Sci. 2022 Oct 5;12(10):1350. doi: 10.3390/brainsci12101350.
Stimulation-induced inhibition is one of the important effects of high-frequency stimulation (HFS) utilized by the therapy of deep brain stimulation (DBS) to treat certain neurological diseases such as epilepsy. In order to explore the stimulation sites to induce inhibition, this study investigated the activation effect of HFS of efferent fibers on the local inhibitory interneurons (IN). Antidromic HFS (A-HFS) of 100 Hz pulses was applied for 2 min at the efferent fibers-the alveus (i.e., the axons of pyramidal neurons) in the hippocampal CA1 region of anesthetized rats. Single unit spikes of INs in local feedback inhibitory circuits, as well as antidromically-evoked population spikes (APS) of pyramidal neurons, were recorded simultaneously in the CA1 region upstream of the stimulation site. Results showed that during the late 60 s of A-HFS, with a substantial suppression in APS amplitudes, the mean firing rate of INs was still significantly greater than the baseline level even when the A-HFS was applied with a weak pulse intensity of 0.08 ± 0.05 mA (9 rats). With a strong pulse intensity of 0.33 ± 0.08 mA (10 rats), the mean firing rate of INs was able to keep at a high level till the end of A-HFS. In addition, the mean latency of IN firing was significantly prolonged during the sustained A-HFS, indicating that alterations had been generated in the pathway to activate INs by the stimulations at efferent fibers. The results suggested that HFS at efferent fibers with various stimulation intensities can modulate the firing of local inhibitory neurons. The finding provides new clues for selecting stimulation sites to enhance inhibition in neural circuits by DBS.
刺激诱导抑制是深部脑刺激（DBS）疗法利用高频刺激（HFS）治疗某些神经系统疾病（如癫痫）的重要效应之一。为了探索诱导抑制的刺激位点，本研究调查了传出纤维高频刺激对局部抑制性中间神经元（IN）的激活作用。对麻醉大鼠海马CA1区的传出纤维——齿状回（即锥体神经元的轴突）施加100Hz脉冲的逆向高频刺激（A-HFS），持续2分钟。在刺激位点上游的CA1区同时记录局部反馈抑制回路中IN的单单位放电，以及锥体神经元的逆向诱发群体放电（APS）。结果显示，在A-HFS的后60秒内，尽管APS幅度大幅抑制，但即使以0.08±0.05mA的弱脉冲强度施加A-HFS（9只大鼠），IN的平均放电率仍显著高于基线水平。以0.33±0.08mA的强脉冲强度（10只大鼠）施加时，IN的平均放电率在A-HFS结束前能保持在较高水平。此外，在持续的A-HFS期间，IN放电的平均潜伏期显著延长，表明传出纤维刺激激活IN的通路发生了改变。结果表明，不同刺激强度的传出纤维高频刺激可调节局部抑制性神经元的放电。这一发现为通过DBS选择刺激位点以增强神经回路中的抑制作用提供了新线索。
