Integrative properties and transfer function of cortical neurons initiating absence seizures in a rat genetic model

摘要

Epileptic seizures result from aberrant cellular and/or synaptic properties that can alter the capacity of neurons to integrate and relay information. During absence seizures, spike-and-wave discharges (SWDs) interfere with incoming sensory inputs and preclude conscious experience. The Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a well-established animal model of absence epilepsy, allows exploration of the cellular basis of this impaired information processing. Here, by combining in vivo electrocorticographic and intracellular recordings from GAERS and control animals, we investigated how the pro-ictogenic properties of seizure-initiating cortical neurons modify their integrative properties and input-output operation during inter-ictal periods and during the spike (S-) and wave (W-) cortical patterns alternating during seizures. In addition to a sustained depolarization and an excessive firing rate in between seizures, ictogenic neurons exhibited a pronounced hyperpolarization-activated depolarization compared to homotypic control neurons. Firing frequency versus injected current relations indicated an increased sensitivity of GAERS cells to weak excitatory inputs, without modifications in the trial-to-trial variability of current-induced firing. During SWDs, the W-component resulted in paradoxical effects in ictogenic neurons, associating an increasedmembrane input resistance with a reduction in the current-evoked firing responses. Conversely, the collapse of cell membrane resistance during the S-component was accompanied by an elevated current-evoked firing relative to W-sequences, which remained, however, lower compared to inter-ictal periods. These findings show a dynamic modulation of ictogenic neurons' intrinsic properties that may alter inter-seizure cortical function and participate in compromising information processing in cortical networks during absences.