Cortical alterations in a model for absence epilepsy and febrile seizures: in vivo findings in mice carrying a human GABA(A)R gamma2 subunit mutation

Neurobiology of Disease
Jens WitschHartwig Spors

Abstract

Childhood absence epilepsy (CAE) is one of the most common forms of epilepsy among children. The study of a large Australian family demonstrated that a point mutation in the gene encoding the gamma2 subunit of the GABA(A) receptor (G2R43Q) leads to an autosomal dominantly inherited form of CAE and febrile seizures (FS). In a transgenic mouse model carrying the gamma2 (R43Q) mutation heterozygous animals recapitulate the human phenotype. In-vitro experiments indicated that this point mutation impairs cortical inhibition and thus increases the likelihood of seizures. Here, using whole-cell (WC) and extracellular (EC) recordings as well as voltage-sensitive dye imaging (VSDI), we systematically searched for an in vivo correlate of cortical alterations caused by the G2R43Q mutation, as suggested by the mentioned in vitro results. We measured spontaneous and whisker-evoked activity in the primary somatosensory cortex and ventral posteriomedial nucleus of the thalamus (VPM) before and after intraperitoneal injection of the ictogenic substance pentylenetetrazol (PTZ) in urethane-anesthetized G2R43Q mice and controls in a blinded setting. Compared to wildtype controls in G2R43Q mice after PTZ injection we found 1.) Increased cortical s...Continue Reading

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Citations

Mar 1, 2012·Neurochemistry International·Francisco CamposJosé Castillo
Nov 2, 2016·Epilepsy Currents·Vanesa Nieto-Estévez, Jenny Hsieh
Nov 17, 2017·The Journal of Pharmacology and Experimental Therapeutics·Shu-Hui Chuang, Doodipala Samba Reddy

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