Nooshin Abdollahi, Amin Kamaleddin Ezabadi, Stephanie Ratte, Steve Prescott
Spikes are usually initiated at the Axon initial segment (AIS), the most excitable site of a neuron.Yet other regions of the neuron are also excitable; indeed, axonal excitability is critical for spike propagation. While there are many studies on somatic and dendritic excitability, axon excitability has yet to be thoroughly investigated in most neurons because the small size of the axon precludes most experiments. There are some recordings from the cut end of axons (i.e. blebs) suggesting that axons do not spike repetitively during sustained depolarization but, instead, spike only at the onset of abrupt depolarization, consistent with class 3 excitability. However, it remains unclear whether transient spiking accurately reflects axon excitability or is an artifact of axon damage. Using a novel optogenetic approach, recent experiments from our lab have shown that axon does indeed have class 3 excitability. Although the optogenetic method is less invasive than bleb recordings, it still has some limitations that necessitated simulations in order to definitively interpret the experimental results. I have built a multicompartment model of a pyramidal neuron with a detailed myelinated axon that reproduces the observed experimental data collected in our lab. The model has helped us confirm the site of spike initiation based on the shape (kinkiness) of spikes recorded in the soma. Simulations also confirmed that even when targeting the axon for photostimulation, a small degree of stray light can hit the dendrites and evoked spikes in the AIS. The results ultimately confirm that unlike spike initiation in the AIS, which relies on class 1 excitability, spike propagation in the axon occurs on the basis of class 3 excitability (Fig. 1).
