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Abstract
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.
GLOSSARY
- GABA=
- γ-aminobutyric acid;
- GABAA=
- γ-aminobutyric acid type A;
- GGE=
- genetic generalized epilepsy;
- IN=
- inhibitory neuron;
- NeuN=
- neuronal nuclei;
- SWD=
- spike-and-wave discharge;
- WT=
- wild-type
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial, page 1290
Supplemental data at Neurology.org
- Received June 17, 2014.
- Accepted in final form November 19, 2014.
- © 2015 American Academy of Neurology
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