Segregation of seizures and spreading depolarization across cortical layers

Abstract

Objective: Cortical spreading depolarization (SD) and seizures are often co-occurring electrophysiological phenomena. However, the cross-layer dynamics of SD during seizures and the effect of SD on epileptic activity across cortical layers remain largely unknown. Methods: We explored the spatial-temporal dynamics of SD and epileptic activity across layers of the rat barrel cortex using direct current silicone probe recordings during flurothyl-induced seizures. Results: SD occurred in half of the flurothyl-evoked seizures. SD always started from the superficial layers and spread downward either through all cortical layers or stopping at the L4/L5 border. In cases without SD, seizures were characterized by synchronized population firing across all cortical layers throughout the entire seizure. However, when SD occurred, epileptic activity was transiently silenced in layers involved with SD but persisted in deeper layers. During partial SD, epileptiform activity persisted in deep layers throughout the entire seizure, with positive signals at the cortical surface reflecting passive sources of population spikes generated in deeper cortical layers. During full SD, the initial phase of SD propagation through the superficial layers was similar to partial SD, with suppression of activity at the superficial layers and segregation of seizures to deep layers. Further propagation of SD to deep layers resulted in a wave of transient suppression of epileptic activity through the entire cortical column. Thus, vertical propagation of SD through the cortical column creates dynamic network states during which epileptiform activity is restricted to layers without SD. Significance: Our results point to the importance of vertical SD spread in the SDrelated depression of epileptiform activity across cortical layers. K E Y W O R D Scortex, DC recordings, EEG, flurothyl, seizure, spreading depression

Spreading depression as an innate antiseizure mechanism

“…Even recurrent SDs were predicted by the extended Hodgkin-Huxley model 9,10 . More importantly, SDs that developed during focal or generalized seizures were associated with seizure termination, after SD seizures did not return for more than 20 min, and when an SD did not develop seizures typically intensified [38][39][40][41] . Similarly, SDs that developed during seizures in the acutely injured human brain was followed by suppression of seizure activity for more than 15 min even when ECoG activity has recovered 8 .…”

Merits and Limitations of Studying Neuronal Depolarization-Dependent Processes Using Elevated External Potassium

“…The difference between in vitro KCl treatments and in vivo SD is that SD events accompany other activity. In epilepsy for instance, SD interacts with synchronous ictal epileptic events and paroxysmal depolarization shifts ( Dreier et al., 2012 ; Kubista et al., 2019 ; Zakharov et al., 2019 ). Thus, it is ambiguous whether the in vivo cellular consequences of SD associated with epilepsy relate to increased synchronous activity, or to the sustained depolarization that follows.…”

Stopped At the Border: Cortical Spreading Depolarization Blocks Seizure Propagation

“…In that regard, the relationship of CSD and seizures is of critical relevance. Theoretically, a seizure might stimulate CSD (as in the case of the present study 3 ) and CSD may counter the excessive electrical activity that occurs during a seizure.…”

“…The current study addresses these questions straight on. Using a rat model of seizures induced by the inhalant convulsant flurothyl, a γ-aminobutyric acid (GABA) antagonist, Zakharov et al 3 used direct current (DC) silicone probe recordings and multiple unit activity recordings to examine electrical activity in the various layers of rat barrel cortex. Rats were immobilized, anesthetized with urethane, and exposed to the inhalant convulsant flurothyl.…”