Synaptic entrainment of ectopic action potential generation in hippocampal pyramidal neurons
Authors: Thome C, Roth FC, Obermayer J, Yanez A, Draguhn A, Egorov AV
CellNetworks People: Draguhn Andreas
Journal: J Physiol. 2018 Aug 24. doi: 10.1113/JP276720.


Ectopic action potentials (EAP) arise at distal locations in axonal fibers 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 EAP is modulated by subthreshold synaptic activity. Somatic subthreshold potentials invade the axonal compartment to considerable distances (>350 μm), whereas spread of axonal sub-threshold potentials to the soma is inefficient. Ectopic spike generation is entrained by conventional synaptic signaling mechanisms. Excitatory synaptic potentials promote EAP, whereas inhibitory synaptic potentials block EAP. 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 (EAP) occur during several neuronal pathologies such as epilepsy, nerve injuries, and inflammation but have also been observed during physiological network activity. EAP 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 signaling during normal and pathological network activity. This article is protected by copyright. All rights reserved.