Augmented Reticular Thalamic Bursting and Seizures in Scn1a-Dravet Syndrome

Stefanie Ritter-Makinson, Alexandra Clemente-Perez, Bryan Higashikubo, Frances S. Cho, Stephanie S. Holden, Eric Bennett, Ana Chkaidze, Oscar H.J. Eelkman Rooda, Marie Coralie Cornet, Freek E. Hoebeek, Kazuhiro Yamakawa, Maria Roberta Cilio, Bruno Delord, Jeanne T. Paz*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Loss of function in the Scn1a gene leads to a severe epileptic encephalopathy called Dravet syndrome (DS). Reduced excitability in cortical inhibitory neurons is thought to be the major cause of DS seizures. Here, in contrast, we show enhanced excitability in thalamic inhibitory neurons that promotes the non-convulsive seizures that are a prominent yet poorly understood feature of DS. In a mouse model of DS with a loss of function in Scn1a, reticular thalamic cells exhibited abnormally long bursts of firing caused by the downregulation of calcium-activated potassium SK channels. Our study supports a mechanism in which loss of SK activity causes the reticular thalamic neurons to become hyperexcitable and promote non-convulsive seizures in DS. We propose that reduced excitability of inhibitory neurons is not global in DS and that non-GABAergic mechanisms such as SK channels may be important targets for treatment.

Original languageEnglish
Pages (from-to)54-64.e6
JournalCell Reports
Issue number1
Publication statusPublished - 2 Jan 2019


  • Animals
  • Disease Models, Animal
  • Epilepsies, Myoclonic/physiopathology
  • Humans
  • Mice
  • Seizures/physiopathology
  • Thalamus/physiopathology


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