Rapid Modulation of Axon Initial Segment Length Influences Repetitive Spike Firing

• 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

SummaryNeurons 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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