Cortical microarchitecture changes in genetic epilepsy.
OBJECTIVE
The human GABAAγ2(R43Q) mutation is associated with genetic epilepsy. Because of the role of γ-aminobutyric acid (GABA) in brain development, we asked whether this epilepsy mutation might affect excitability by changing cortical cytoarchitecture.


METHODS
We used a mouse model harboring a heterozygous R43Q missense mutation in the GABAA receptor subunit γ2, as identified in a family with absence epilepsy and febrile seizures. Three-dimensional quantification of immunostained neurons (NeuN), inhibitory neurons (GABA), and inhibitory neuron subpopulations (calretinin, parvalbumin, and calbindin) was performed in fiducial somatosensory cortical columns of seizure-naive GABAAγ2(R43Q) and control mice.


RESULTS
Of note, the densities of GABA-, calretinin-, parvalbumin-, and calbindin-containing neurons were increased, and somewhat perplexing, the ratio between putative excitatory and inhibitory neurons was decreased in GABAAγ2(R43Q) mice. Differences were detected in a layer-specific manner with greater overall effects in layers 2/3, 5, and 6, as compared with layers 1 and 4.


CONCLUSIONS
Our results suggest that the γ2(R43Q) mutation significantly affects cortical microcircuitry in the cortex of this model of human genetic epilepsy.
From The Florey Institute of Neuroscience and Mental Health (V.C.W., M.Y.-S.L., S.P.) and Centre for Neuroscience (S.P.), University of Melbourne; and Epilepsy Research Centre and Department of Medicine (S.F.B.), University of Melbourne, Austin Health, Australia.
Verena C
VC
Wimmer
From The Florey Institute of Neuroscience and Mental Health (V.C.W., M.Y.-S.L., S.P.) and Centre for Neuroscience (S.P.), University of Melbourne; and Epilepsy Research Centre and Department of Medicine (S.F.B.), University of Melbourne, Austin Health, Australia.
Melody Y-S
MY
Li
From The Florey Institute of Neuroscience and Mental Health (V.C.W., M.Y.-S.L., S.P.) and Centre for Neuroscience (S.P.), University of Melbourne; and Epilepsy Research Centre and Department of Medicine (S.F.B.), University of Melbourne, Austin Health, Australia.
Samuel F
SF
Berkovic
From The Florey Institute of Neuroscience and Mental Health (V.C.W., M.Y.-S.L., S.P.) and Centre for Neuroscience (S.P.), University of Melbourne; and Epilepsy Research Centre and Department of Medicine (S.F.B.), University of Melbourne, Austin Health, Australia. spetrou@unimelb.edu.au.
Steven
S
Petrou
D000818:Animals; D002452:Cell Count; D004827:Epilepsy / Q000235:genetics / Q000473:pathology*; D005260:Female; D006965:Hyperplasia / Q000473:pathology; D008297:Male; D051379:Mice; D020125:Mutation, Missense; D009474:Neurons / Q000473:pathology; D061848:Optical Imaging; D011963:Receptors, GABA-A / Q000235:genetics*; D013003:Somatosensory Cortex / Q000473:pathology*
D011963:Receptors, GABA-A