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Spike‐wave discharges in absence epilepsy: segregation of electrographic components reveals distinct pathways of seizure activity
Author(s) -
Terlau Jonas,
Yang JenqWei,
Khastkhodaei Zeinab,
Seidenbecher Thomas,
Luhmann Heiko J.,
Pape HansChristian,
Lüttjohann Annika
Publication year - 2020
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp279483
Subject(s) - neuroscience , thalamus , spike and wave , excitatory postsynaptic potential , epilepsy , local field potential , electroencephalography , electrophysiology , spike (software development) , somatosensory system , physics , psychology , computer science , inhibitory postsynaptic potential , software engineering
Key points The major electrophysiological hallmarks of absence seizures are spike and wave discharges (SWDs), consisting of a sharp spike component and a slow wave component. In a widely accepted scheme, these components are functionally coupled and reflect an iterative progression of neuronal excitation during the spike and post‐excitatory silence during the wave. In a genetic rat model of absence epilepsy, local pharmacological inhibition of the centromedian thalamus (CM) selectively suppressed the spike component, leaving self‐contained waves in epidural recordings. Thalamic inputs induced activity in cortical microcircuits underlying the spike component, while intracortical oscillations generated the wave component. Based on these findings, we propose a model in which oscillatory waves provide adequate time windows for integration of thalamocortical inputs and feedback responses during generation of a synchronized SWD.Abstract Spike and wave discharges (SWDs) are the electrographic hallmark of absence seizures and the major diagnostic criterion for childhood absence epilepsy (CAE). In a widely accepted scheme, the alternating sequence of spikes and waves reflects an iterative progression of neuronal excitation during the spike component and post‐excitatory silence during the wave component. Here we challenge this view by showing that these two components are not necessarily coupled. In a genetic rat model of CAE, self‐contained waves occurred in motor cortex in synchrony with SWDs in the somatosensory system during blockade of afferent input from the thalamus. Current‐source density analyses of multi‐site local field potentials (LFPs) revealed layer‐specific activity, in which thalamic inputs induced a sequence of cellular‐synaptic events underlying the spike component, while intracortical oscillations generated the wave component. These findings indicate novel principles of SWDs, where oscillatory cortical waves provide adequate time windows for integration of thalamocortical inputs and feedback responses during generation of seizure activity.