Abstract
Dravet syndrome (DS) is a childhood disorder associated with loss-of-function mutations
in SCN1A and is characterized by frequent seizures and severe cognitive impairment. Animal
studies have revealed new insights into the mechanisms by which mutations in this
gene, encoding the type I voltage-gated sodium channel (Nav1.1), may lead to seizure activity and cognitive dysfunction. In this review, we further
consider the function of fast-spiking GABAergic neurons, one cell type particularly
affected by these mutations, in the context of the temporal coordination of neural
activity subserving cognitive functions. We hypothesize that disruptions in GABAergic
firing may directly contribute to the poor cognitive outcomes in children with DS,
and discuss the therapeutic implications of this possibility.
Highlights
- Dravet syndrome is a childhood disorder associated with mutations in SCN1A.
- It is characterized by frequent seizures and severe cognitive impairment.
- We propose that dysfunction in GABAergic neurons leads to altered brain oscillations.
- Both seizures and altered oscillations may contribute to cognitive impairment.
Keywords
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Article info
Publication history
Accepted:
November 27,
2011
Received in revised form:
November 26,
2011
Received:
August 22,
2011
Identification
Copyright
© 2011 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
