Temperature elevation increases GABA(A)-mediated cortical inhibition in a mouse model of genetic epilepsy

Elisa L Hill; Suzanne Hosie; Rachel S Mulligan; Kay L Richards; Philip J Davies; Celine M Dube; Tallie Z Baram; Christopher A Reid; Mathew V Jones; Steven Petrou

Journal article

Temperature elevation increases GABA(A)-mediated cortical inhibition in a mouse model of genetic epilepsy

Elisa L Hill, Suzanne Hosie, Rachel S Mulligan, Kay L Richards, Philip J Davies, Celine M Dube, Tallie Z Baram, Christopher A Reid, Mathew V Jones, Steven Petrou

EPILEPSIA | WILEY-BLACKWELL | 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 GABA(A) γ2(R43Q) mice displayed a lower temperature threshold for thermal seizures as compared to wild-type littermates. Temperature-dependent internalization of GABA(A) γ2(R43Q)-containing receptors has been proposed as a mechanism underlying febrile seizure genesis in patients with this mutation. We tested this idea using the GABA(A) γ2(R43Q) knockin mouse model and analyzed GABAergic miniature postsynaptic inhibitory currents (mIPSCs) in acute brain slices after exposure to varying temperatures. Incuba..

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University of Melbourne Researchers

Steven Petrou Author Florey Department of Neuroscience and Mental Health

Elisa Hill Author Anatomy and Physiology

Christopher Reid Author Medicine - Austin Health

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Febrile Seizures (FS) affect 3% of children aged 0.5 - 6 yrs and have been proposed as an indicator of severe forms of adult generalized epi..

Grants

Awarded by National Health and Medical Research Council (NHMRC) of Australia

Awarded by National Institute of Health

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).