Synchronous hippocampal bursting reveals network excitability defects in an epilepsy gene mutation

Santosh Helekar, Jeffrey L. Noebels

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

A mutation at the tottering locus (tg, recessive, on chromosome 8) stimulates noradrenergic locus coeruleus axon terminal outgrowth and predisposes the brain to generalized spike-wave epilepsy in the young mouse. In an isolated synaptic circuit studied in vitro, the hyperinnervated mutant hippocampal pyramidal neurons respond normally when individually activated; however, latent neuronal signaling defects emerge during synchronous network bursting, revealing two conditional excitability phenotypes: a voltage-dependent prolongation of a complex synaptic response, the paroxysmal depolarizing shift, and a β-adrenoreceptor-linked attenuation of the afterhyperpolarization. In this target brain region, the tg locus transforms neuronal excitability without altering measured intrinsic membrane properties, indicating that gene control of inherited epileptic traits may be mediated in part by activity-dependent modulation of network behavior favoring synchronous neuronal firing.

Original languageEnglish (US)
Pages (from-to)4736-4740
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number11
DOIs
StatePublished - Jun 1 1991

Keywords

  • Afterhyperpolarization
  • Cornu ammonis region 3 pyramidal neurons
  • Norepinephrine
  • Paroxysmal depolarizing shift
  • Tottering mouse

ASJC Scopus subject areas

  • General
  • Genetics

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