Institute of Physiology and Pathophysiology, Department of Neurophysiology, Heidelberg University, 69120, Heidelberg, Germany.
Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, 0317, Oslo, Norway.
J Physiol. 2018 Nov;596(21):5237-5249. doi: 10.1113/JP276720. Epub 2018 Sep 19.
Ectopic action potentials (EAPs) arise at distal locations in axonal fibres and are often associated with neuronal pathologies such as epilepsy or nerve injury, but they also occur during physiological network conditions. This study investigates whether initiation of such EAPs is modulated by subthreshold synaptic activity. Somatic subthreshold potentials invade the axonal compartment to considerable distances (>350 μm), whereas spread of axonal subthreshold potentials to the soma is inefficient. Ectopic spike generation is entrained by conventional synaptic signalling mechanisms. Excitatory synaptic potentials promote EAPs, whereas inhibitory synaptic potentials block EAPs. The modulation of ectopic excitability depends on propagation of somatic voltage deflections to the axonal EAP initiation site. Synaptic modulation of EAP initiation challenges the view of the distal axon being independent of synaptic activity and may contribute to mechanisms underlying fast network oscillations and pathological network activity.
While most action potentials are generated at the axon initial segment, they can also be triggered at more distal sites along the axon. Such ectopic action potentials (EAPs) occur during several neuronal pathologies such as epilepsy, nerve injuries and inflammation but have also been observed during physiological network activity. EAPs propagate antidromically towards the somato-dendritic compartment where they modulate synaptic plasticity. Here we investigate the converse signal direction: do somato-dendritic synaptic potentials affect the generation of ectopic spikes? We measured anti- and orthodromic spikes in the soma and axon of mouse hippocampal CA1 pyramidal cells. We found that synaptic potentials propagate reliably through the axon, causing significant voltage transients at distances >350 μm. At these sites, excitatory input efficiently facilitated EAP initiation in distal axons and, conversely, inhibitory input suppressed EAP initiation. Our data reveal a new mechanism by which ectopically generated spikes can be entrained by conventional synaptic signalling during normal and pathological network activity.
异位动作电位 (EAP) 出现在轴突纤维的远端位置，通常与癫痫或神经损伤等神经元病变有关，但也出现在生理网络条件下。本研究探讨了亚阈突触活动是否调节这种 EAP 的产生。体细胞亚阈电位侵入轴突隔室的距离很大 (>350μm)，而轴突亚阈电位向体细胞的传播效率不高。异位尖峰的产生与传统的突触信号机制有关。兴奋性突触电位促进 EAP，而抑制性突触电位抑制 EAP。异位兴奋性的调节取决于体细胞电压偏移向轴突 EAP 起始位点的传播。EAP 起始的突触调制挑战了远端轴突独立于突触活动的观点，并可能有助于快速网络振荡和病理网络活动的机制。
虽然大多数动作电位是在轴突起始段产生的，但它们也可以在轴突的更远部位触发。这种异位动作电位 (EAP) 发生在癫痫、神经损伤和炎症等几种神经元病变期间，但也在生理网络活动期间观察到。EAP 向体树突隔室逆行传播，在那里它们调节突触可塑性。在这里，我们研究了相反的信号方向：体树突突触电位是否会影响异位尖峰的产生？我们测量了小鼠海马 CA1 锥体神经元体和轴突中的反和顺向尖峰。我们发现，突触电位可靠地通过轴突传播，在 >350μm 的距离处引起显著的电压瞬变。在这些部位，兴奋性输入有效地促进了远端轴突中的 EAP 起始，相反，抑制性输入抑制了 EAP 起始。我们的数据揭示了一种新的机制，即在正常和病理网络活动期间，异位产生的尖峰可以通过传统的突触信号来触发。
