Deep brain stimulation (DBS) is a promising neuromodulation therapy, but the neurophysiological mechanisms of DBS remain unclear. In awake mice, we performed high-speed membrane voltage fluorescence imaging of individual hippocampal CA1 neurons during DBS delivered at 40 Hz or 140 Hz, free of electrical interference. DBS powerfully depolarized somatic membrane potentials without suppressing spike rate, especially at 140 Hz. Further, DBS paced membrane voltage and spike timing at the stimulation frequency and reduced timed spiking output in response to hippocampal network theta-rhythmic (3–12 Hz) activity patterns. To determine whether DBS directly impacts cellular processing of inputs, we optogenetically evoked theta-rhythmic membrane depolarization at the soma. We found that DBS-evoked membrane depolarization was correlated with DBS-mediated suppression of neuronal responses to optogenetic inputs. These results demonstrate that DBS produces powerful membrane depolarization that interferes with the ability of individual neurons to respond to inputs, creating an informational lesion.

深部脑刺激 (DBS) 是一种很有前途的神经调节疗法，但 DBS 的神经生理学机制仍不清楚。在清醒的小鼠中，我们在 DBS 期间以 40 Hz 或 140 Hz 的频率对单个海马 CA1 神经元进行了高速膜电压荧光成像，没有电干扰。DBS 在不抑制尖峰率的情况下有效地去极化体细胞膜电位，尤其是在 140 Hz 时。此外，DBS 在刺激频率下调节膜电压和尖峰时间，并减少定时尖峰输出以响应海马网络 θ 节律 (3–12 Hz) 活动模式。为了确定 DBS 是否直接影响输入的细胞处理，我们在体细胞处通过光遗传学诱发了 θ 节律膜去极化。我们发现 DBS 诱发的膜去极化与 DBS 介导的对光遗传学输入的神经元反应抑制相关。这些结果表明 DBS 产生强大的膜去极化，干扰单个神经元响应输入的能力，从而产生信息损伤。