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Summary   Objective  Genetic alterations have been identified in the   CACNA 1H  gene, encoding the Ca V 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 Ca V 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 .    Methods  Pathophysiological contributions of Ca V 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.    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 SWD s and correlating with the expression of a Ca V 3.2 mutation‐sensitive splice variant. In vivo knock‐down of Ca V 3.2 using direct thalamic injection of lipid nanoparticles containing Ca V 3.2 dicer small interfering (Dsi) RNA normalized  TRN  burst‐firing, and in free‐moving  GAERS  significantly shortened seizures.    Significance  This supports a role for  TRN  Ca V 3.2 T‐type channels in propagating thalamocortical network seizures and setting the pacemaking frequency of  SWD s.

Ca V 3.2 drives sustained burst‐firing, which is critical for absence seizure propagation in reticular thalamic neurons