title: A candidate mechanism underlying the variance of interictal spike propagation.
abstract: Synchronous activation of neural networks is an important physiological mechanism, and dysregulation of synchrony forms the basis of epilepsy. We analyzed the propagation of synchronous activity through chronically epileptic neural networks. Electrocorticographic recordings from epileptic patients demonstrate remarkable variance in the pathways of propagation between sequential interictal spikes (IISs). Calcium imaging in chronically epileptic slice cultures demonstrates that pathway variance depends on the presence of GABAergic inhibition and that spike propagation becomes stereotyped following GABA receptor blockade. Computer modeling suggests that GABAergic quenching of local network activations leaves behind regions of refractory neurons, whose late recruitment forms the anatomical basis of variability during subsequent network activation. Targeted path scanning of slice cultures confirmed local activations, while ex vivo recordings of human epileptic tissue confirmed the dependence of interspike variance on GABA-mediated inhibition. These data support the hypothesis that the paths by which synchronous activity spreads through an epileptic network change with each activation, based on the recent history of localized activity that has been successfully inhibited.
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
authors.forename: Helen R
authors.initials: HR
authors.lastname: Sabolek
authors.forename: Waldemar B
authors.initials: WB
authors.lastname: Swiercz
authors.forename: Kyle P
authors.initials: KP
authors.lastname: Lillis
authors.forename: Sydney S
authors.initials: SS
authors.lastname: Cash
authors.forename: Gilles
authors.initials: G
authors.lastname: Huberfeld
authors.forename: Grace
authors.initials: G
authors.lastname: Zhao
authors.forename: Linda
authors.initials: L
authors.lastname: Ste Marie
authors.forename: Stéphane
authors.initials: S
authors.lastname: Clemenceau
authors.forename: Greg
authors.initials: G
authors.lastname: Barsh
authors.forename: Richard
authors.initials: R
authors.lastname: Miles
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Staley
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000328:Adult; D000818:Animals; D004569:Electroencephalography / Q000379:methods; D004827:Epilepsy / Q000503:physiopathology*; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009924:Organ Culture Techniques; D011897:Random Allocation; D051381:Rats