Yuan Yue, Feng Zhouyan, Yang Gangsheng, Ye Xiangyu, Wang Zhaoxiang
Key Lab of Biomedical Engineering for Education Ministry, College of Biomedical Engineering and Instrumentation Science, Zhejiang University, Hangzhou, China.
Front Neurosci. 2022 Jun 10;16:881426. doi: 10.3389/fnins.2022.881426. eCollection 2022.
High-frequency stimulation (HFS) of electrical pulses has been used to treat certain neurological diseases in brain with commonly utilized effects within stimulation periods. Post-stimulation effects after the end of HFS may also have functions but are lack of attention. To investigate the post-stimulation effects of HFS, we performed experiments in the rat hippocampal CA1 region . Sequences of 1-min antidromic-HFS (A-HFS) were applied at the alveus fibers. To evaluate the excitability of the neurons, separated orthodromic-tests (O-test) of paired pulses were applied at the Schaffer collaterals in the period of baseline, during late period of A-HFS, and following A-HFS. The evoked potentials of A-HFS pulses and O-test pulses were recorded at the stratum pyramidale and the stratum radiatum of CA1 region by an electrode array. The results showed that the antidromic population spikes (APS) evoked by the A-HFS pulses persisted through the entire 1-min period of 100 Hz A-HFS, though the APS amplitudes decreased significantly from the initial value of 9.9 ± 3.3 mV to the end value of 1.6 ± 0.60 mV. However, following the cessation of A-HFS, a silent period without neuronal firing appeared before the firing gradually recovered to the baseline level. The mean lengths of both silent period and recovery period of pyramidal cells (21.9 ± 22.9 and 172.8 ± 91.6 s) were significantly longer than those of interneurons (11.2 ± 8.9 and 45.6 ± 35.9 s). Furthermore, the orthodromic population spikes (OPS) and the field excitatory postsynaptic potentials (fEPSP) evoked by O-tests at ∼15 s following A-HFS decreased significantly, indicating the excitability of pyramidal cells decreased. In addition, when the pulse frequency of A-HFS was increased to 200, 400, and 800 Hz, the suppression of neuronal activity following A-HFS decreased rather than increased. These results indicated that the neurons with axons directly under HFS can generate a post-stimulation suppression of their excitability that may be due to an antidromic invasion of axonal A-HFS to somata and dendrites. The finding provides new clues to utilize post-stimulation effects generated in the intervals to design intermittent stimulations, such as closed-loop or adaptive stimulations.
电脉冲的高频刺激（HFS）已被用于治疗脑部的某些神经疾病，在刺激期间具有常见的作用。HFS结束后的刺激后效应可能也有功能，但缺乏关注。为了研究HFS的刺激后效应，我们在大鼠海马CA1区进行了实验。在齿状回纤维处施加1分钟的逆向HFS（A-HFS）序列。为了评估神经元的兴奋性，在基线期、A-HFS后期以及A-HFS之后，在Schaffer侧支施加成对脉冲的分离正向测试（O测试）。通过电极阵列在CA1区的锥体层和辐射层记录A-HFS脉冲和O测试脉冲的诱发电位。结果表明，A-HFS脉冲诱发的逆向群体峰电位（APS）在100Hz A-HFS的整个1分钟期间持续存在，尽管APS幅度从初始值9.9±3.3mV显著下降到终值1.6±0.60mV。然而，在A-HFS停止后，在放电逐渐恢复到基线水平之前出现了一个无神经元放电的沉默期。锥体细胞的沉默期和恢复期的平均长度（21.9±22.9和172.8±91.6秒）明显长于中间神经元（11.2±8.9和45.6±35.9秒）。此外，在A-HFS后约15秒时，O测试诱发的正向群体峰电位（OPS）和场兴奋性突触后电位（fEPSP）显著降低，表明锥体细胞的兴奋性降低。此外，当A-HFS的脉冲频率增加到200、400和800Hz时，A-HFS后神经元活动的抑制减弱而非增强。这些结果表明，轴突直接处于HFS下的神经元可产生对其兴奋性的刺激后抑制，这可能是由于轴突A-HFS向胞体和树突的逆向侵入。这一发现为利用间隔期产生的刺激后效应来设计间歇性刺激，如闭环或自适应刺激提供了新线索。
