Our main interest in single neuron modeling is the initiation of spikes. Vertebrate neurons communicate primarily with action potentials or « spikes », which is why a basic neurophysiological question is to understand precisely what makes neurons spike. The question also has clinical importance, because a number of pathologies are dysfunctions of neural excitability (e.g. epilepsy and multiple sclerosis), and because neural prostheses rely on the precise stimulation of neurons (e.g. cochlear implants and retinal prostheses). Finally, the topic has a central role in theoretical neuroscience, as this is one area where we have biophysical models that have strong predictive power. It also connects with metabolism, in particular the regulation and modulation of ionic channels and energy consumption.
Please contact us if you are interested in working on these topics (romain.brette[at]inserm.fr).
In most vertebrate neurons, spikes initiate in the axonal initial segment, 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. 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.
An often neglected aspect of spike initiation is that spike threshold is not a fixed quantity, but varies on short and long timescales. On short timescales, we found using biophysical models that most data could be explained by the inactivation of Na channels, possibly in conjunction with the subthreshold opening of K channels, and we proposed a threshold equation that predicts the value of spike threshold as a function of biophysical properties.