Cell Reports
Volume 13, Issue 6, 10 November 2015, Pages 1233-1245
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Article
Rapid Modulation of Axon Initial Segment Length Influences Repetitive Spike Firing

https://doi.org/10.1016/j.celrep.2015.09.066Get rights and content
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Highlights

  • Structural plasticity at the axon initial segment can occur within hours

  • Ankyrin-G and sodium channel distributions shorten after 3 hr of elevated activity

  • Rapid plasticity depends on calcineurin signaling opposed by CDK5

  • All else being equal, AIS shortening correlates with lowered neuronal excitability

Summary

Neurons implement a variety of plasticity mechanisms to alter their function over timescales ranging from seconds to days. One powerful means of controlling excitability is to directly modulate the site of spike initiation, the axon initial segment (AIS). However, all plastic structural AIS changes reported thus far have been slow, involving days of neuronal activity perturbation. Here, we show that AIS plasticity can be induced much more rapidly. Just 3 hr of elevated activity significantly shortened the AIS of dentate granule cells in a calcineurin-dependent manner. The functional effects of rapid AIS shortening were offset by dephosphorylation of voltage-gated sodium channels, another calcineurin-dependent mechanism. However, pharmacological separation of these phenomena revealed a significant relationship between AIS length and repetitive firing. The AIS can therefore undergo a rapid form of structural change over timescales that enable interactions with other forms of activity-dependent plasticity in the dynamic control of neuronal excitability.

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This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

2

Present address: Gladstone Institute of Neurological Disease, 1650 Owens Street, San Francisco, CA 94158-2261, USA

3

Present address: Department of Biology, Utrecht University, Padualaan 8, 3584CH Utrecht, the Netherlands

4

Co-first author