The developmental evolution of the seizure phenotype and cortical inhibition in mouse models of juvenile myoclonic epilepsy.

ABSTRACT: The GABA(A) receptor (GABA(A)R) α1 subunit mutation, A322D, causes autosomal dominant juvenile myoclonic epilepsy (JME). Previous in vitro studies demonstrated that A322D elicits α1(A322D) protein degradation and that the residual mutant protein causes a dominant-negative effect on wild type GABA(A)Rs. Here, we determined the effects of heterozygous A322D knockin (Het(α1)AD) and deletion (Het(α1)KO) on seizures, GABA(A)R expression, and motor cortex (M1) miniature inhibitory postsynaptic currents (mIPSCs) at two developmental time-points, P35 and P120. Both Het(α1)AD and Het(α1)KO mice experience absence seizures at P35 that persist at P120, but have substantially more frequent spontaneous and evoked polyspike wave discharges and myoclonic seizures at P120. Both mutant mice have increased

SUBMITTER: Arain F 

PROVIDER: S-EPMC4641014 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature