Corticothalamic 5-9 Hz oscillations are more pro-epileptogenic than sleep spindles in rats.

Abstract

Absence-related spike-and-wave discharges (SWDs) occur in the thalamocortical system during quiet wakefulness or drowsiness. In feline generalized penicillin epilepsy, SWDs develop from sleep spindles. In contrast, in genetic absence epilepsy rats from Strasbourg (GAERS), SWDs develop from wake-related 5-9 Hz oscillations, which are distinct from spindle oscillations (7-15 Hz). Since these two oscillation types share common frequency bands and may contribute to SWD genesis, it is important to compare their thalamic cellular mechanisms. Under neuroleptic analgesia, in GAERS and control non-epileptic rats barbiturates abolished both SWDs and 5-9 Hz oscillations but increased the incidence of spindle-like oscillations. Within the thalamocortical circuit 5-9 Hz oscillations occurred more coherently than spindle-like oscillations. Intracellular events associated with 5-9 Hz and spindle-like oscillations were distinctively different in both thalamic relay and reticular neurons. In both cell types, SWDs and 5-9 Hz oscillations emerged from a significantly more depolarized membrane potential than spindle-like oscillations. In relay neurons, 5-9 Hz oscillations were mainly characterized by a rhythmic depolarization, which occurred during a tonic hyperpolarization and which could trigger an apparent low-threshold Ca2+ potential, whereas spindle-like oscillations were characterized by a rhythmic hyperpolarization. In reticular cells, SWDs and 5-9 Hz oscillations occurred during a tonic hyperpolarization, whereas spindle-like oscillations occurred during a long-lasting depolarizing envelope. The difference in the intracellular events between 5-9 Hz and spindle-like oscillations and similarities between 5-9 Hz oscillations and SWDs indicate that in GAERS, 5-9 Hz oscillations are more pro-epileptogenic than spindle-like oscillations. In conclusion, the present study strongly supports the hypothesis that SWDs in GAERS are generated by a wake-related corticothalamic resonance, and not by sleep-related, hypersynchronous, spindle-like activity originating in the thalamus.