Neocortical seizures: initiation, development and cessation

Different forms of electrical paroxysms in experimental animals mimic the patterns of absence seizures associated with spike-wave complexes at approximately 3 Hz and of Lennox-Gastaut seizures with spike-wave or polyspike-wave complexes at approximately 1.5-2.5 Hz, intermingled with fast runs at 10-20 Hz. Both these types of electrical seizures are preferentially generated during slow-wave sleep. Here, we challenge the hypothesis of a subcortical pacemaker that would account for suddenly generalized spike-wave seizures as well as the idea of an exclusive role of synaptic excitation in the generation of paroxysmal depolarizing components, and we focus on three points, based on multiple intracellular and field potential recordings in vivo that are corroborated by some clinical studies: (a) the role of neocortical bursting neurons, especially fast-rhythmic-bursting neurons, and of very fast oscillations (ripples, 80-200 Hz) in seizure initiation; (b) the cortical origin of both these types of electrical paroxysms, the synaptic propagation of seizures from one to other, local and distant, cortical sites, finally reaching the thalamus, where the synchronous cortical firing excites thalamic reticular inhibitory neurons and thus leads to steady hyperpolarization and phasic inhibitory postsynaptic potentials in a majority of thalamocortical neurons, which might explain the obliteration of signals from the external world and the unconsciousness during absence seizures; and (c) the cessation of seizures, whose cellular mechanisms have only begun to be investigated and remain an open avenue for research.