Sharpness of Spike Initiation in Neurons Explained by Compartmentalization

In cortical neurons, spikes are initiated in the axon initial segment. Seen at the soma, they appear surprisingly sharp. A standard explanation is that the current coming from the axon becomes sharp as the spike is actively backpropagated to the soma. However, sharp initiation of spikes is also seen in the input–output properties of neurons, and not only in the somatic shape of spikes; for example, cortical neurons can transmit high frequency signals. An alternative hypothesis is that Na channels cooperate, but it is not currently supported by direct experimental evidence. I propose a simple explanation based on the compartmentalization of spike initiation. When Na channels are placed in the axon, the soma acts as a current sink for the Na current. I show that there is a critical distance to the soma above which an instability occurs, so that Na channels open abruptly rather than gradually as a function of somatic voltage.Author Summary: Spike initiation determines how the combined inputs to a neuron are converted to an output. Since the pioneering work of Hodgkin and Huxley, it is known that spikes are generated by the opening of sodium channels with depolarization. According to this standard theory, these channels should open gradually when the membrane potential increases, but spikes measured at the soma appear to suddenly rise from rest. This apparent contradiction has triggered a controversy about the origin of spike “sharpness.” This study shows with biophysical modelling that if sodium channels are placed in the axon rather than in the soma, they open all at once when the somatic membrane potential exceeds a critical value. This work explains the sharpness of spike initiation and provides another demonstration that morphology plays a critical role in neural function.