Cortical microarchitecture changes in genetic epilepsy

Neurology. 2015 Mar 31;84(13):1308-16. doi: 10.1212/WNL.0000000000001415. Epub 2015 Mar 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Count
  • Epilepsy / genetics
  • Epilepsy / pathology*
  • Female
  • Hyperplasia / pathology
  • Male
  • Mice
  • Mutation, Missense
  • Neurons / pathology
  • Optical Imaging
  • Receptors, GABA-A / genetics*
  • Somatosensory Cortex / pathology*


  • Receptors, GABA-A