Augmented Reticular Thalamic Bursting and Seizures in Scn1a-Dravet Syndrome.
Dravet syndrome
Nav1.1
SK current
Scn1a
epilepsy
optogenetics
reticular thalamic nucleus
seizures
thalamocortical circuits
thalamocortical oscillations
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
02 01 2019
02 01 2019
Historique:
received:
06
09
2018
revised:
07
11
2018
accepted:
03
12
2018
entrez:
4
1
2019
pubmed:
4
1
2019
medline:
20
3
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30605686
pii: S2211-1247(18)31929-6
doi: 10.1016/j.celrep.2018.12.018
pmc: PMC6555418
mid: NIHMS1517849
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
54-64.e6Subventions
Organisme : NINDS NIH HHS
ID : R00 NS078118
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS096369
Pays : United States
Commentaires et corrections
Type : ErratumIn
Type : CommentIn
Informations de copyright
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
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