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 Ca_V2.3 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 Ca_V2.3 knockout (KO) mouse model using local field potential (LFP), and electroencephalographic (EEG) recordings. The duration of cumulative SWDs was significantly decreased in Ca_V2.3 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 Ca_V2.3 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.