title: Rapid Modulation of Axon Initial Segment Length Influences Repetitive Spike Firing.
abstract: 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.
authors.affiliation: MRC Centre for Developmental Neurobiology, King's College London, 4(th) Floor, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Evans
authors.affiliation: MRC Centre for Developmental Neurobiology, King's College London, 4(th) Floor, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
authors.forename: Adna S
authors.initials: AS
authors.lastname: Dumitrescu
authors.affiliation: MRC Centre for Developmental Neurobiology, King's College London, 4(th) Floor, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
authors.forename: Dennis L H
authors.initials: DLH
authors.lastname: Kruijssen
authors.affiliation: MRC Centre for Developmental Neurobiology, King's College London, 4(th) Floor, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
authors.forename: Samuel E
authors.initials: SE
authors.lastname: Taylor
authors.affiliation: MRC Centre for Developmental Neurobiology, King's College London, 4(th) Floor, New Hunt's House, Guy's Campus, London SE1 1UL, UK. Electronic address: matthew.grubb@kcl.ac.uk.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Grubb
mesh_terms: D000200:Action Potentials; D000818:Animals; D017487:Ankyrins / Q000378:metabolism; D001369:Axons / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D019703:Calcineurin / Q000378:metabolism; D002478:Cells, Cultured; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity; D051381:Rats; D017208:Rats, Wistar; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism
chemical_list: D017487:Ankyrins; D061566:Voltage-Gated Sodium Channels; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse; D019703:Calcineurin