Synchronous Hippocampal Bursting Reveals Network Excitability Defects in an Epilepsy Gene Mutation

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1991 Jun 1

PMID 2052555

Citations 4

Authors

S A Helekar

J L Noebels

Affiliations

Soon will be listed here.

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 beta-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.

Citing Articles

Abnormal excitability and episodic low-frequency oscillations in the cerebral cortex of the tottering mouse.

Cramer S, Popa L, Carter R, Chen G, Ebner T J Neurosci. 2015; 35(14):5664-79.

PMID: 25855180 PMC: 4388925. DOI: 10.1523/JNEUROSCI.3107-14.2015.

Altered functional expression of Purkinje cell calcium channels precedes motor dysfunction in tottering mice.

Erickson M, Haburcak M, Smukler L, Dunlap K Neuroscience. 2007; 150(3):547-55.

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Enhanced G protein-dependent modulation of excitatory synaptic transmission in the cerebellum of the Ca2+ channel-mutant mouse, tottering.

Zhou Y, Turner T, Dunlap K J Physiol. 2003; 547(Pt 2):497-507.

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Single locus mutations in mice expressing generalized spike-wave absence epilepsies.

Noebels J Ital J Neurol Sci. 1995; 16(1-2):107-11.

PMID: 7642343 DOI: 10.1007/BF02229082.

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