These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Early developmental alterations of CA1 pyramidal cells in Dravet syndrome.
    Author: Jones SP, O'Neill N, Carpenter JC, Muggeo S, Colasante G, Kullmann DM, Lignani G.
    Journal: Neurobiol Dis; 2024 Oct 15; 201():106688. PubMed ID: 39368670.
    Abstract:
    Dravet Syndrome (DS) is most often caused by heterozygous loss-of-function mutations in the voltage-gated sodium channel gene SCN1A (Nav1.1), resulting in severe epilepsy and neurodevelopmental impairment thought to be cause by reduced interneuron excitability. However, recent studies in mouse models suggest that interneuron dysfunction alone does not completely explain all the cellular and network impairments seen in DS. Here, we investigated the development of the intrinsic, synaptic, and network properties of CA1 pyramidal cells in a DS model prior to the appearance of overt seizures. We report that CA1 pyramidal cell development is altered by heterozygous reduction of Scn1a, and propose that this is explained by a period of reduced intrinsic excitability in early postnatal life, during which Scn1a is normally expressed in hippocampal pyramidal cells. We also use a novel ex vivo model of homeostatic plasticity to show an instability in homeostatic response during DS epileptogenesis. This study provides evidence for the early effects of Scn1a haploinsufficiency in pyramidal cells in contributing to the pathophysiology of DS.
    [Abstract] [Full Text] [Related] [New Search]