In most vertebrate neurons, spikes initiate in the axonal initial segment (AIS), a small structure near the soma, packed with ionic channels and other proteins. Based on biophysical analysis, we have proposed that this situation makes normal spike initiation (i.e. through depolarizing the soma) different from the textbook account (Brette 2013). In the textbook account, spikes are initiated through the interplay between Na+ and K+ transmembrane currents, when Na+ current increases faster with voltage than K+ current. We propose instead that spikes are initiated through the interplay between Na+ current and axial resistive current flowing between AIS and soma. We called this account the compartmentalization of spike initiation because it is manifested by a large voltage gradient across the two sites specifically at spike initiation. One very important consequence is that Na channels open abruptly as a function of somatic voltage, making the integrate-and-fire model a more accurate phenomenological model of spike initiation than the single-compartment Hodgkin-Huxley model (Brette 2015). It explains why integrate-and-fire models are so good at predicting the responses of neurons to somatically injected currents, which we (and other labs) found out using optimization techniques (Rossant et al. 2010; 2011).
- Brette R (2013). Sharpness of spike initiation in neurons explained by compartmentalization. PLoS Comp Biol, doi: 10.1371/journal.pcbi.1003338.
- Brette R (2015). What Is the Most Realistic Single-Compartment Model of Spike Initiation? PLoS Comput Biol. 2015 Apr 9;11(4):e1004114.
- Rossant C, Goodman DF, Platkiewicz J and Brette R (2010). Automatic fitting of spiking neuron models to electrophysiological recordings. Front. Neuroinform. doi:10.3389/neuro.11.002.2010
- Rossant C, Goodman DF, Fontaine B, Platkiewicz J, Magnusson AK and Brette R (2011). Fitting neuron models to spike trains.Front Neurosci. 5:9. doi: 10.3389/fnins.2011.00009.