Abdollahi Nooshin, Xie Yu-Feng, Ratté Stéphanie, Prescott Steven A
Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.
Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
J Neurosci. 2025 Mar 19;45(12):e1889242025. doi: 10.1523/JNEUROSCI.1889-24.2025.
Action potentials (spikes) are regenerated at each node of Ranvier during saltatory transmission along a myelinated axon. The high density of voltage-gated sodium channels required by nodes to reliably transmit spikes increases the risk of ectopic spike generation in the axon. Here we show that ectopic spiking is avoided because K1 channels prevent nodes from responding to slow depolarization; instead, axons respond selectively to rapid depolarization because K1 channels implement a high-pass filter. To characterize this filter, we compared spike initiation properties in the soma and axon of CA1 pyramidal neurons from mice of both sexes, using spatially restricted photoactivation of channelrhodopsin-2 (ChR2) to evoke spikes in either region while simultaneously recording at the soma. Somatic photostimulation evoked repetitive spiking whereas axonal photostimulation evoked transient spiking. Blocking K1 channels converted the axon photostimulation response to repetitive spiking and encouraged spontaneous ectopic spike initiation in the axon. According to computational modeling, the high-pass filter implemented by K1 channels matches the axial current waveform associated with saltatory conduction, enabling axons to faithfully transmit digital signals by maximizing their signal-to-noise ratio for this task. Specifically, a node generates a single spike only when rapidly depolarized, which is precisely what occurs during saltatory conduction when a pulse of axial current (triggered by a spike occurring at the upstream node) reaches the next node. The soma and axon use distinct spike initiation mechanisms (filters) appropriate for the task required of each region, namely, analog-to-digital transduction in the soma versus digital signal transmission in the axon.
在沿有髓轴突的跳跃式传导过程中，动作电位（峰电位）在每个郎飞结处再生。郎飞结可靠地传导峰电位所需的高密度电压门控钠通道增加了轴突中异位峰电位产生的风险。我们在此表明，异位峰电位的产生得以避免是因为K1通道可防止郎飞结对缓慢的去极化做出反应；相反，轴突对快速去极化具有选择性反应，因为K1通道实现了一个高通滤波器。为了表征这个滤波器，我们比较了雌雄小鼠CA1锥体神经元的胞体和轴突中的峰电位起始特性，利用视紫红质-2（ChR2）的空间限制性光激活在任一区域诱发峰电位，同时在胞体处进行记录。胞体光刺激诱发重复性峰电位，而轴突光刺激诱发短暂性峰电位。阻断K1通道将轴突光刺激反应转变为重复性峰电位，并促使轴突中自发产生异位峰电位。根据计算模型，K1通道实现的高通滤波器与跳跃式传导相关的轴向电流波形相匹配，使轴突能够通过最大化此任务的信噪比来忠实地传输数字信号。具体而言，一个郎飞结仅在快速去极化时产生单个峰电位，这恰好是跳跃式传导过程中发生的情况，即当轴向电流脉冲（由上游郎飞结处发生的峰电位触发）到达下一个郎飞结时。胞体和轴突使用适合每个区域所需任务的不同峰电位起始机制（滤波器），即胞体中的模拟到数字转换与轴突中的数字信号传输。
