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

Significance Action potentials initiate in the axon initial segment (AIS), close to the soma. Previous experimental findings suggested that a distal shift in AIS position reduces excitability, but theoretical work predicts the opposite. A distal shift in AIS position corresponds to an elevation of axial resistance ( R a ) between soma and AIS. We modified R a and measured the voltage threshold (V th ) of action potentials in the soma of cortical neurons. Increasing R a by mechanically pinching the axon hillock lowered V th by ∼6 mV, whereas decreasing R a by substituting internal ions with higher mobility elevated V th . Thus, excitability increases with axial resistance and therefore with a distal shift of the AIS.