Neuron Morphology Influences Axon Initial Segment Plasticity.

Allan T Gulledge,Jaime J Bravo

doi:10.1523/eneuro.0085-15.2016

Allan T Gulledge, Jaime J Bravo

Open Access

https://doi.org/10.1523/eneuro.0085-15.2016

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Journal: eNeuro	Publication Date: Jan 1, 2016
Citations: 80	License type: cc-by

Affiliation: Dartmouth–Hitchcock Medical Center, Dartmouth College

Abstract

In most vertebrate neurons, action potentials are initiated in the axon initial segment (AIS), a specialized region of the axon containing a high density of voltage-gated sodium and potassium channels. It has recently been proposed that neurons use plasticity of AIS length and/or location to regulate their intrinsic excitability. Here we quantify the impact of neuron morphology on AIS plasticity using computational models of simplified and realistic somatodendritic morphologies. In small neurons (e.g., dentate granule neurons), excitability was highest when the AIS was of intermediate length and located adjacent to the soma. Conversely, neurons having larger dendritic trees (e.g., pyramidal neurons) were most excitable when the AIS was longer and/or located away from the soma. For any given somatodendritic morphology, increasing dendritic membrane capacitance and/or conductance favored a longer and more distally located AIS. Overall, changes to AIS length, with corresponding changes in total sodium conductance, were far more effective in regulating neuron excitability than were changes in AIS location, while dendritic capacitance had a larger impact on AIS performance than did dendritic conductance. The somatodendritic influence on AIS performance reflects modest soma-to-AIS voltage attenuation combined with neuron size-dependent changes in AIS input resistance, effective membrane time constant, and isolation from somatodendritic capacitance. We conclude that the impact of AIS plasticity on neuron excitability will depend largely on somatodendritic morphology, and that, in some neurons, a shorter or more distally located AIS may promote, rather than limit, action potential generation.

Highlights

We demonstrate that somatodendritic morphology will dictate both the magnitude and direction of excitability changes occurring in response to axon initial segment (AIS) plasticity
Action potentials in most vertebrate neurons are initiated in a specialized region of proximal axon known as the axon initial segment (AIS)
Our results demonstrate that AIS performance depends heavily on somatodendritic morphology, and suggest that, in some neurons, plastic changes in AIS length and location that are typically predicted to reduce neuron excitability may instead promote action potential initiation

Summary

Introduction

Action potentials in most vertebrate neurons are initiated in a specialized region of proximal axon known as the axon initial segment (AIS). For instance, prolonged periods of enhanced excitatory drive reversibly translocate the AIS away from the soma (Grubb and Burrone, 2010; Evans et al, 2013; Muir and Kittler, 2014) These shifts in AIS location were correlated with decreased intrinsic excitability, as reflected in higher somatic current thresholds (rheobase currents) for action potential initiation (Grubb and Burrone, 2010; Evans et al, 2013). In both the auditory (Kuba et al, 2014) and visual (Gutzmann et al, 2014) systems, postnatal sensory experience sculpts AIS morphology, while experimental manipulations of sensory input drive dynamic modifications of AIS architecture (Gutzmann et al, 2014; Kuba et al, 2014) that correlate with changes in neuron excitability (Kuba et al, 2010)

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