CaV3.2 drives sustained burst-firing, which is critical for absence seizure propagation in reticular thalamic neurons

Stuart M. Cain, John R. Tyson, Hyun Beom Choi, Rebecca Ko, Paulo J.C. Lin, Jeffrey M. Ledue, Kim L. Powell, Louis Philippe Bernier, Ravi L. Rungta, Yi Yang, Pieter R. Cullis, Terence J. O'Brien, Brian A. Macvicar, Terrance P. Snutch

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31 Citations (Scopus)


Objective: Genetic alterations have been identified in the CACNA1H gene, encoding the CaV3.2 T-type calcium channel in patients with absence epilepsy, yet the precise mechanisms relating to seizure propagation and spike-wave-discharge (SWD) pacemaking remain unknown. Neurons of the thalamic reticular nucleus (TRN) express high levels of CaV3.2 calcium channels, and we investigated whether a gain-of-function mutation in the Cacna1h gene in Genetic Absence Epilepsy Rats from Strasbourg (GAERS) contributes to seizure propagation and pacemaking in the TRN. Methods: Pathophysiological contributions of CaV3.2 calcium channels to burst firing and absence seizures were assessed in vitro using acute brain slice electrophysiology and quantitative real-time polymerase chain reaction (PCR) and in vivo using free-moving electrocorticography recordings. Results: TRN neurons from GAERS display sustained oscillatory burst-firing that is both age- and frequency-dependent, occurring only in the frequencies overlapping with GAERS SWDs and correlating with the expression of a CaV3.2 mutation-sensitive splice variant. In vivo knock-down of CaV3.2 using direct thalamic injection of lipid nanoparticles containing CaV3.2 dicer small interfering (Dsi) RNA normalized TRN burst-firing, and in free-moving GAERS significantly shortened seizures. Significance: This supports a role for TRN CaV3.2 T-type channels in propagating thalamocortical network seizures and setting the pacemaking frequency of SWDs.

Original languageEnglish
Pages (from-to)778-791
Number of pages14
Issue number4
Publication statusPublished - Apr 2018


  • Absence epilepsy
  • Low threshold spike
  • T-type calcium channel
  • Thalamocortical

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