Ictal heterogeneity in the awake cortex
Absence seizures consist of a sudden and brief impairment of consciousness accompanied by a lack of voluntary movements and generalized, bilaterally synchronous ‘spike and wave discharges’ (SWDs) at 2.5-4 Hz in the EEG. While generally considered relatively benign because of their non-convulsive nature and the large incidence of remittance in early adulthood recent studies show that 30% of children with absence seizures are pharmaco-resistant and 60% are affected by severe neuropsychiatric comorbid conditions. Thus, the mechanisms of generation, maintenance, generalization and termination is important, but has remained relatively unexplored. Similar SWDs are exhibited by diverse genetic rodent models including the behaviorally, physiologically and pharmacologically fully validated GAERS rats (Genetically Epileptic Rats from Strasbourg) providing direct evidence for the crucial involvement of cortico-thalamo-cortical networks in SWD generation. Most previous studies have used anesthetized preparations and revealed an important contribution from various types of neurons in the infragranular layers of the cortical initiation network (CIN) in the somatosensory cortex. We monitored the ictal and interictal membrane potential and action potential output of various neurons in the CIN and various thalamic nuclei of awake behaving rats and revealed a marked heterogeneity of neuronal activities in contrast to the more stereotypical ictal activity observed in anesthetized preparations. The pre-ictal membrane potential of some cortical neurons shows rhythmic oscillations correlated to the proximal membrane potential. The rate and rhythmicity of some neurons in the CIN is altered before the onset of electrographic seizures. Some thalamocortical neurons are involved in the generation and others in the generalization of SWDs. Taken together our results provide new insights into the mechanism of SWD generation and generalization and highlight the importance of neuronal recordings obtained in awake-behaving animals.