Ca(v)2.3 Channels Are Critical for Oscillatory Burst Discharges in the Reticular Thalamus and Absence Epilepsy

Abstract

Neurons of the reticular thalamus (RT) display oscillatory burst discharges that are believed to be critical for thalamocortical network oscillations related to absence epilepsy. Ca2+-dependent mechanisms underlie such oscillatory discharges. However, involvement of high-voltage activated (HVA) Ca2+ channels in this process has been discounted. We examined this issue closely using mice deficient for the HVA Ca(v)2.3 channels. In brain slices of Ca(v)2.3(-/-), a hyperpolarizing current injection initiated a low-threshold burst of spikes in RI neurons; however, subsequent oscillatory burst discharges were severely suppressed, with a significantly reduced slow afterhyperpolarization (AHP). Consequently, the lack of Ca(v)2.3 resulted in a marked decrease in the sensitivity of the animal to gamma-butyrolactone-induced absence epilepsy. Local blockade of Ca(v)2.3 channels in the RT mimicked the results of Ca(v)2.3(-/-) mice. These results provide strong evidence that Ca(v)2.3 channels are critical for oscillatory burst discharges in RT neurons and for the expression of absence epilepsy.