Theoretical relation between axon initial segment geometry and excitability

Abstract

8In most vertebrate neurons, action potentials are triggered at the distal end of the axon initial segment 9 (AIS). Both position and length of the AIS vary across and within neuron types, with activity, 10 development and pathology. What is the impact of AIS geometry on excitability? Direct empirical 11 assessment has proven difficult because of the many potential confounding factors. Here we carried a 12principled theoretical analysis to answer this question. We provide a simple formula relating AIS 13 geometry and sodium conductance density to the somatic voltage threshold. A distal shift of the AIS 14 normally produces a (modest) increase in excitability, but we explain how this pattern can reverse if a 15 hyperpolarizing current is present at the AIS, due to resistive coupling with the soma. This work 16 provides a theoretical tool to assess the significance of structural AIS plasticity for electrical function.

Brief sensory deprivation triggers cell type-specific structural and functional plasticity in olfactory bulb neurons

“…In contrast, changes in AIS length have a much clearer corollary. Experimental and theoretical results are in close agreement that, all else being equal, a shorter AIS leads to decreased excitability (Evans et al, 2015;Goethals and Brette, 2019;Grubb and Burrone, 2010;Gulledge and Bravo, 2016;Höfflin et al, 2017;Jamann et al, 2020;Kuba et al, 2010;Pan-Vazquez et al, 2020;Sohn et al, 2019;Wefelmeyer et al, 2015). Our data showing brief sensory deprivationinduced AIS shortening and decreased excitability in OB DA neurons are entirely consistent with this coherent picture.…”

“…One key function of the AIS, which houses voltage-activated sodium channels at high density, is to initiate action potentials (Kole et al, 2007). Previous experimental evidence (e.g., (Evans et al, 2015;Kuba et al, 2010)) and computational models (see, e.g., (Goethals and Brette, 2020;Gulledge and Bravo, 2016;Hamada et al, 2016)) have shown that alterations in AIS length, all else being equal, are associated with decreases in neuronal excitability. So does the experience-dependent decrease in AIS length we observe in axon-bearing DA cells correlate with a reduced ability to fire action potentials?…”