Temperature elevation increases GABAA-mediated cortical inhibition in a mouse model of genetic epilepsy

EL Hill; S Hosie; RS Mulligan; KL Richards; PJ Davies; CM Dubé; TZ Baram; CA Reid; MV Jones; S Petrou

Journal article

Temperature elevation increases GABAA-mediated cortical inhibition in a mouse model of genetic epilepsy

EL Hill, S Hosie, RS Mulligan, KL Richards, PJ Davies, CM Dubé, TZ Baram, CA Reid, MV Jones, S Petrou

Epilepsia | Published : 2011

DOI: 10.1111/j.1528-1167.2010.02914.x

Abstract

A missense mutation (R43Q) in the γ2 subunit of the γ-aminobutyric acid (GABA)A receptor is associated with generalized (genetic) epilepsy with febrile seizures plus (GEFS+). Heterozygous GABAAγ2(R43Q) mice displayed a lower temperature threshold for thermal seizures as compared to wild-type littermates. Temperature-dependent internalization of GABAAγ2(R43Q)-containing receptors has been proposed as a mechanism underlying febrile seizure genesis in patients with this mutation. We tested this idea using the GABAAγ2(R43Q) knockin mouse model and analyzed GABAergic miniature postsynaptic inhibitory currents (mIPSCs) in acute brain slices after exposure to varying temperatures. Incubation of sli..

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University of Melbourne Researchers

Elisa Hill Author

Christopher Reid Author

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Grants

Awarded by National Institute of Neurological Disorders and Stroke

Funding Acknowledgements

This study was supported by a New Investigator project grant from the National Health and Medical Research Council (NHMRC) of Australia (509224; to EH), an NHMRC program grant (400121; to SP), the Caitlin's Fund for Epilepsy Research (to EH), and the National Institute of Health (NS35439; to TZB and CMD and NS046378 to MVJ).