Rapid Modulation of Axon Initial Segment Length Influences Repetitive Spike Firing

Mark D. Evans, Adna S. Dumitrescu, Dennis L H Kruijssen, Samuel E. Taylor, Matthew S. Grubb*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

112 Citations (Scopus)
380 Downloads (Pure)


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.

Original languageEnglish
Pages (from-to)1233-1245
Number of pages13
JournalCell Reports
Issue number6
Early online date29 Oct 2015
Publication statusPublished - 10 Nov 2015


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