CaV 3.2 drives sustained burst-firing, which is critical for absence seizure propagation in reticular thalamic neurons

Epilepsia
Stuart M CainTerrance P Snutch

Abstract

Genetic alterations have been identified in the CACNA1H gene, encoding the CaV 3.2 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 CaV 3.2 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. Pathophysiological contributions of CaV 3.2 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. 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 CaV 3.2 mutation-sensitive splice variant. In vivo knock-down of CaV 3.2 using direct thalamic injection of lipid nanoparticles containing CaV 3.2 dicer small interfering (Dsi) RNA normalized TRN burs...Continue Reading

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Citations

Dec 5, 2019·Brain : a Journal of Neurology·Qing-Long MiaoJeffrey L Noebels
Jun 21, 2019·Journal of Medical Genetics·Norbert Weiss, Gerald W Zamponi
May 22, 2020·Brain : a Journal of Neurology·Vincenzo CrunelliFrançois David
Jul 9, 2020·Pflügers Archiv : European journal of physiology·Philippe LoryArnaud Monteil
Mar 17, 2021·The Journal of Comparative Neurology·Nidhi Vasant Desai, Carmen Varela
Apr 20, 2021·British Journal of Pharmacology·Erika K HardingMichael E Hildebrand

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Methods Mentioned

BETA
transfection

Software Mentioned

Ca
GAERS

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