CaV2.3 channels in the mouse central medial thalamic nucleus are essential for thalamocortical oscillations and spike wave discharges

Voltage-gated calcium channels are important for thalamocortical (TC) oscillations related to spike-wave discharges (SWDs) during absence seizures. The role of CaV2.3 R-type channels expressed in the thalamic intralaminar complex in SWDs, however, is not well studied. We investigated pharmacologically induced SWDs from the central medial thalamus (CMT) and somatosensory cortex in a CaV2.3 knockout (KO) mouse model using local field potential (LFP), and electroencephalographic (EEG) recordings. The duration of cumulative SWDs was significantly decreased in CaV2.3 KO mice compared with wild-type (WT) mice. A characteristic increase in the delta and theta waves was observed in both the CMT and somatosensory cortex during SWDs with delta (1-4 Hz) band TC synchronization increasing only in WT animals. Specifically, in the KO mice, LFPs recorded from the CMT showed no significant changes in the delta band and a significant decrease in the theta (4-8 Hz) band, and cortical EEG recordings showed a significant increase in the delta band, but no changes in the theta band. The baseline TC phase synchronization in the delta band was also more pronounced in the CaV2.3 KO mice than in WT mice. These findings suggest that R-type calcium channels in the CMT play a crucial role in sustaining and promoting the oscillatory activity of the TC network during absence seizures.