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 CaV2.3 channels. In brain slices of CaV2.3-/-, a hyperpolarizing current injection initiated a low-threshold burst of spikes in RT neurons; however, subsequent oscillatory burst discharges were severely suppressed, with a significantly reduced slow afterhyperpolarization (AHP). Consequently, the lack of CaV2.3 resulted in a marked decrease in the sensitivity of the animal to γ-butyrolactone-induced absence epilepsy. Local blockade of CaV2.3 channels in the RT mimicked the results of CaV2.3-/- mice. These results provide strong evidence that CaV2.3 channels are critical for oscillatory burst discharges in RT neurons and for the expression of absence epilepsy.
Bibliographical noteFunding Information:
We thank Chanki Kim, M.A. Aslam, Gireesh G., Sungsoo Jang, Soojung Lee, Il-hwan Choe, and Seung-eun Lee for technical as well as intellectual support. This work was supported by the National Honor Scientist Program of the Korean Government, and the WCI program of Korea Institute of Science and Technology.
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