Mourra Devry, Cavalieri Angela M, Casey Madison M, Sahin Mesut, Lang Eric J
Department of Neuroscience and Physiology, Grossman School of Medicine, NYU Neuroscience Institute, New York University, New York, NY, 10016, USA.
Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA.
Cerebellum. 2025 Jan 2;24(1):21. doi: 10.1007/s12311-024-01756-0.
Cerebellar transcranial alternating current stimulation (ctACS) has the potential to be an appealing, non-invasive treatment option for psychiatric and neurological disorders. However, realization of this potential has been limited by gaps in our knowledge of how ctACS affects cerebellar output on single cell and population levels. Previously, we showed that AC stimulation applied to the cerebellar surface produced a strong, frequency-dependent modulation of Purkinje cell (PC) and cerebellar nuclear (CN) cell activity. Here, to approximate more closely the ctACS conditions, we investigated how AC stimulation applied to the external skull surface overlying crus 1 altered PC and CN activity in anesthetized adult female Sprague-Dawley rats. PC and CN activity showed a frequency-dependent modulation in response to ctACS at frequencies ranging from 0.5 to 80 Hz. A unimodal response was seen for most PCs across all frequencies, whereas most CN cells transitioned to bimodal patterns as stimulus frequency increased. The frequency-dependence of the phases of the local minima of the CN cell modulation were consistent with CN cells being driven synaptically by PC activity. Furthermore, comparison of responses with ipsilateral and contralateral placement of the stimulus electrode with respect to the recording site showed that the strength and pattern of the entrainment depended on the stimulus electrode location, suggesting that ctACS electrode placement could be used to target specific cerebellar output channels. In sum, the results show that transcranial stimulation of the cerebellar cortex can modulate cerebellar output, which has potential implications for its use in treating neurological and psychiatric disorders.
小脑经颅交流电刺激（ctACS）有可能成为一种有吸引力的、用于治疗精神疾病和神经疾病的非侵入性治疗选择。然而，由于我们对ctACS如何在单细胞和群体水平上影响小脑输出的了解存在空白，这一潜力的实现受到了限制。此前，我们表明，施加于小脑表面的交流电刺激对浦肯野细胞（PC）和小脑核（CN）细胞的活动产生了强烈的、频率依赖性的调制。在此，为了更接近ctACS的条件，我们研究了施加于覆盖小脑 Crus 1 的颅骨外表面的交流电刺激如何改变麻醉成年雌性 Sprague-Dawley 大鼠的 PC 和 CN 活动。在 0.5 至 80 Hz 的频率范围内，PC 和 CN 活动对 ctACS 表现出频率依赖性调制。在所有频率下，大多数 PC 呈现单峰反应，而随着刺激频率增加，大多数 CN 细胞转变为双峰模式。CN 细胞调制局部最小值相位的频率依赖性与 CN 细胞由 PC 活动突触驱动一致。此外，将刺激电极相对于记录部位同侧和对侧放置时的反应进行比较，结果表明夹带的强度和模式取决于刺激电极的位置，这表明 ctACS 电极放置可用于靶向特定的小脑输出通道。总之，结果表明对小脑皮质的经颅刺激可调节小脑输出，这对其在治疗神经疾病和精神疾病中的应用具有潜在意义。
