Year: 2019
Type: article
Abstract: 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.
Source: Cell Reports
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: National Science Foundation, American Epilepsy Society, Belgian American Educational Foundation, National Sleep Foundation, Gladstone Institutes, Achievement Rewards for College Scientists Foundation, Dravet Syndrome Foundation, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Epilepsy Society, National Institutes of Health, National Institute of Neurological Disorders and Stroke
OpenAlex ID: W2907719702