title: Axon initial segment structural plasticity in animal models of genetic and acquired epilepsy.
abstract: A novel form of neuronal plasticity, occurring at the axon initial segment (AIS), has recently been described. Lengthening of the AIS and movement away from the soma are consequences of changes in neuronal input and result in alterations in neuronal excitability. We hypothesised that AIS plasticity may play a role in epilepsy, due to chronic changes in neuronal activity. Immunohistochemistry and confocal microscopy were used to analyse AIS length and position in pyramidal neurons in deep layer 5 of the somatosensory cortex from 5 mice with genetic epilepsy and 4 controls, and from 3 rats subjected to amygdala kindling and 3 controls. The effect of a subtle alteration of AIS position was modelled computationally. We identified a difference in the position of the AIS in animals with seizures: in mice the AIS was positioned 0.2 μm further away from the soma, and in rats the AIS was positioned 0.6 μm closer to the soma compared with controls. Computational modelling indicated that a subtle alteration in AIS position could result in a change in action potential firing threshold. The identification of AIS plasticity in animal models of epilepsy is significant in furthering our understanding of the pathophysiological mechanisms involved in this disorder.
authors.affiliation: Ion Channels & Disease Group, Epilepsy Division, The Florey Institute of Neuroscience and Mental Health, Kenneth Myer Building, Cnr Genetics Lane and Royal Parade, Parkville, Victoria 3010, Australia.
authors.forename: Rosemary C
authors.initials: RC
authors.lastname: Harty
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Kim
authors.forename: Evan A
authors.initials: EA
authors.lastname: Thomas
authors.forename: Lisa
authors.initials: L
authors.lastname: Cardamone
authors.forename: Nigel C
authors.initials: NC
authors.lastname: Jones
authors.forename: Steven
authors.initials: S
authors.lastname: Petrou
authors.forename: Verena C
authors.initials: VC
authors.lastname: Wimmer
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology*; D003198:Computer Simulation; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000009:adverse effects; D004569:Electroencephalography; D004827:Epilepsy / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D007696:Kindling, Neurologic; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008959:Models, Neurological; D009154:Mutation / Q000235:genetics; D009473:Neuronal Plasticity / Q000502:physiology*; D028061:Phosphate Transport Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000235:genetics; D015222:Sodium Channels / Q000378:metabolism; D013003:Somatosensory Cortex / Q000473:pathology*
chemical_list: C498769:Ankh protein, mouse; D028061:Phosphate Transport Proteins; D011963:Receptors, GABA-A; D015222:Sodium Channels
keywords: Amygdala kindling; Axon initial segment; Childhood absence epilepsy; Epilepsy; Seizure; Structural neuronal plasticity