Neural excitability increases with axonal resistance between soma and axon initial segment.

The position of the axon initial segment (AIS) is thought to play a critical role in neuronal excitability. Previous experimental studies have found that a distal shift in AIS position correlates with a reduction in excitability. Yet theoretical work has suggested the opposite, because of increased electrical isolation. A distal shift in AIS position corresponds to an elevation of axial resistance R a We therefore examined how changes in R a at the axon hillock impact the voltage threshold (Vth) of the somatic action potential in L5 pyramidal neurons. Increasing R a by mechanically pinching the axon between the soma and the AIS was found to lower Vth by ∼6 mV. Conversely, decreasing R a by substituting internal ions with higher mobility elevated Vth All R a -dependent changes in Vth could be reproduced in a Hodgkin-Huxley compartmental model. We conclude that in L5 pyramidal neurons, excitability increases with axial resistance and therefore with a distal shift of the AIS.