T-type Ca²⁺ channels in absence epilepsy

Abstract

Low-voltage-activated T-type Ca²⁺ channels are highly expressed in the thalamocortical circuit, suggesting that they play a role in this brain circuit. Indeed, low-threshold burst firing mediated by T-type Ca²⁺ channels has long been implicated in the synchronization of the thalamocortical circuit. Over the past few decades, the conventional view has been that rhythmic burst firing mediated by T-type channels in both thalamic reticular nuclie (TRN) and thalamocortical (TC) neurons are equally critical in the generation of thalamocortical oscillations during sleep rhythms and spike-wave-discharges (SWDs). This review broadly investigates recent studies indicating that even though both TRN and TC nuclei are required for thalamocortical oscillations, the contributions of T-type channels to TRN and TC neurons are not equal in the genesis of sleep spindles and SWDs. T-type channels in TC neurons are an essential component of SWD generation, whereas the requirement for TRN T-type channels in SWD generation remains controversial at least in the GBL model of absence seizures. Therefore, a deeper understanding of the functional consequences of modulating each T-type channel subtype could guide the development of therapeutic tools for absence seizures while minimizing side effects on physiological thalamocortical oscillations. This article is part of a Special Issue entitled: Calcium channels.