Seizure-related activity of intralaminar thalamic neurons in a genetic model of absence epilepsy.

Absence seizures are characterized by bilateral spike-and-wave discharges (SWDs) in thalamo-cortical circuits. In view of clinical studies indicating a critical involvement of intralaminar thalamic nuclei, we thought it timely to characterize the specific role and activity patterns of the respective neurons. Electrocorticographic (ECoG), intracellular, and unit activity recordings were performed in vivo from intralaminar thalamic neurons of the centrolateral (CL) and the paracentral (PC) thalamic nucleus in an established genetic rat model of absence epilepsy (WAG/Rij). Neurons in PC are depolarized to produce tonic series of action potentials at seizure-free episodes, and are rhythmically silenced concomitant with SWDs in a spike-locked manner. Rebound from spike-locked inhibition is associated with a transient increase in action potential activity. Neurons in CL possess a relatively negative membrane potential with overall low electrogenic activity at seizure-free episodes and generate burst-like discharges during SWDs that are locked to the decaying phase of the spike component on the ECoG. The SWD-locked membrane responses reverse close to the presumed chloride equilibrium potential, indicating GABA(A) receptor-mediated inhibitory postsynaptic potentials (IPSPs), with cell-type specific differences in polarity. In PC neurons, hyperpolarizing IPSPs result in spike-locked silencing of tonic firing and rebound burst discharges, while in CL neurons, IPSPs are depolarizing and trigger low-threshold burst firing likely mediated by a t-type Ca(2+) conductance. These data show a unique pattern of rhythmic SWD-locked IPSPs in PC and CL associated with paroxysms apt to impose a transient dysfunctional state to thalamo-striato-prefrontocortical networks during absence seizures.