Activity of Thalamic Reticular Neurons during Spontaneous Genetically Determined Spike and Wave Discharges

This study reports the first intracellular recordings obtained during spontaneous, genetically determined spike and wave discharges (SWDs) in nucleus reticularis thalami (NRT) neurons from the genetic absence epilepsy rats from Strasbourg (GAERS), a model that closely reproduces the typical features of childhood absence seizures. A SWD started with a large hyperpolarization, which was independent of the preceding firing, and decreased in amplitude but did not reverse in polarity up to potentials >/= -90 mV. This hyperpolarization and the slowly decaying depolarization that terminated a SWD were unaffected by recording with KCl-filled electrodes. The prolonged (up to 15 action potentials), high-frequency bursts present during SWDs were tightly synchronized between adjacent neurons, correlated with the EEG spike component, and generated by a low-threshold Ca(2+) potential, which, in turn, was brought about by the summation of high-frequency, small-amplitude depolarizing potentials. Fast hyperpolarizing IPSPs were not detected either during or in the absence of SWDs. Recordings with KCl-filled electrodes, however, showed a more depolarized resting membrane potential and a higher background firing, whereas the SWD-associated bursts had a longer latency to the EEG spike and a lower intraburst frequency. This novel finding demonstrates that spontaneous genetically determined SWDs occur in the presence of intra-NRT lateral inhibition. The unmasking of these properties in the GAERS NRT confirms their unique association with spontaneous genetically determined SWDs and thus their likely involvement in the pathophysiological processes of the human condition.