Transsynaptic entrainment of cerebellar nuclear cells by alternating currents in a frequency dependent manner.
Transsynaptic entrainment of cerebellar nuclear cells by alternating currents in a frequency dependent manner.
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DOI：
10.3389/fnins.2023.1282322
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发表时间：
2023
影响因子：
4.3
通讯作者：
Sahin, Mesut
中科院分区：
文献类型：
--
作者：
Kang, Qi;Lang, Eric J.;Sahin, Mesut
经颅交流电刺激（tACS）是一种非侵入性神经调节技术，正在临床上测试用于治疗各种神经疾病。研究tACS潜在机制的动物研究很少，在小脑中几乎不存在。在本研究中，我们将10-400 Hz交流电（AC）应用于氯胺酮/甲苯噻嗪麻醉大鼠的小脑皮质。小脑核（CN）细胞的放电活动是跨突触夹带的AC刺激的频率在强度和频率依赖性的方式。有趣的是，存在调制的调谐曲线，其中中频（100和150 Hz）的频率更有效，尽管每个CN细胞的最大调制的刺激频率不同，对刺激幅度有轻微的依赖性。CN尖峰夹带着相对于AC刺激周期的几毫秒的延迟。这些短的潜伏期和CN细胞的跨突触调制可以在如此高的频率下发生，强烈表明在毫秒时间尺度上的PC简单尖峰同步是CN细胞夹带的潜在机制。这些结果表明，阈下AC刺激可以诱导这样的PC锋电位同步，而不诉诸于阈上脉冲刺激的精确定时。通过皮层刺激的深CN细胞的跨突触夹带可以帮助在tACS应用中将刺激电流保持在安全限度内，从而允许开发tACS作为深部小脑刺激的替代治疗。我们的研究结果也提供了一个可能的解释人类试验小脑刺激的功能影响的tACS的频率依赖性。
Transcranial alternating current stimulation (tACS) is a non-invasive neuromodulation technique that is being tested clinically for treatment of a variety of neural disorders. Animal studies investigating the underlying mechanisms of tACS are scarce, and nearly absent in the cerebellum. In the present study, we applied 10–400 Hz alternating currents (AC) to the cerebellar cortex in ketamine/xylazine anesthetized rats. The spiking activity of cerebellar nuclear (CN) cells was transsynaptically entrained to the frequency of AC stimulation in an intensity and frequency-dependent manner. Interestingly, there was a tuning curve for modulation where the frequencies in the midrange (100 and 150 Hz) were more effective, although the stimulation frequency for maximum modulation differed for each CN cell with slight dependence on the stimulation amplitude. CN spikes were entrained with latencies of a few milliseconds with respect to the AC stimulation cycle. These short latencies and that the transsynaptic modulation of the CN cells can occur at such high frequencies strongly suggests that PC simple spike synchrony at millisecond time scales is the underlying mechanism for CN cell entrainment. These results show that subthreshold AC stimulation can induce such PC spike synchrony without resorting to supra-threshold pulse stimulation for precise timing. Transsynaptic entrainment of deep CN cells via cortical stimulation could help keep stimulation currents within safety limits in tACS applications, allowing development of tACS as an alternative treatment to deep cerebellar stimulation. Our results also provide a possible explanation for human trials of cerebellar stimulation where the functional impacts of tACS were frequency dependent.
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4.2
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通讯作者：
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