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Reduced cortical inhibition in a mouse model of familial childhood absence epilepsy
Open accessAbstract
Mutations in the GABA A receptor γ2 subunit are associated with childhood absence epilepsy and febrile seizures. To understand better the molecular basis of absence epilepsy in man, we developed a mouse model harboring a γ2 subunit point mutation (R43Q) found in a large Australian family. Mice heterozygous for the mutation demonstrated behavioral arrest associated with 6-to 7-Hz spike-and-wave discharges, which are blocked by ethosuximide, a first-line treatment for absence epilepsy in man. Seizures in the mouse showed an abrupt onset at around age 20 days corresponding to the childhood nature of this disease. Reduced cell surface expression of γ2(R43Q) was seen in heterozygous mice in the absence of any change in α1 subunit surface expression, ruling out a dominant-negative effect. GABA A-mediated synaptic currents recorded from cortical pyramidal neurons revealed a small but significant reduction that was not seen in the reticular or ventrobasal thalamic nuclei. We hypothesize that a subtle reduction in cortical inhibition underlies childhood absence epilepsy seen in humans harboring the R43Q mutation.
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Hensch, T. K. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1787 · Cited by 2,323
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Receptor trafficking and synaptic plasticity
Collingridge, G. L., Isaac, J. T. R., & Wang, Y. T. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1556 · Cited by 1,046
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Stellwagen, D., Beattie, E. C., Seo, J. Y., & Malenka, R. C. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.4486-04.2005 · Cited by 985
Laminar processing in the visual cortical column.
Hirsch, J. A., & Martinez, L. M. (2006) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2006.06.014 · Cited by 120
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Enhanced tonic GABAA inhibition in typical absence epilepsy
Cope, D. W., Di Giovanni, G., Fyson, S. J., Orbán, G., Errington, A. C., Lőrincz, M. L., Gould, T. M., Carter, D. A., & Crunelli, V. (2009) · Nature Medicine · doi:10.1038/nm.2058 · Cited by 431
Ion Channels in Genetic Epilepsy: From Genes and Mechanisms to Disease-Targeted Therapies
Oyrer, J., Maljevic, S., Scheffer, I. E., Berkovic, S. F., Petrou, S., & Reid, C. A. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014456 · Cited by 315
Self-citationSeparating Neural Oscillations from Aperiodic 1/f Activity: Challenges and Recommendations
Gerster, M., Waterstraat, G., Litvak, V., Lehnertz, K., Schnitzler, A., Florin, E., Curio, G., & Nikulin, V. (2022) · Neuroinformatics · doi:10.1007/s12021-022-09581-8 · Cited by 253
Papale, L. A., Beyer, B., Jones, J. M., Sharkey, L. M., Tufik, S., Epstein, M., Letts, V. A., Meisler, M. H., Frankel, W. N., & Escayg, A. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp081 · Cited by 127
Metadata
- Authors
- Tan, H. O., Reid, C. A., Single, F. N., Davies, P. J., Chiu, C., Murphy, S., Clarke, A. L., Dibbens, L., Krestel, H., Mulley, J. C., Jones, M. V., Seeburg, P. H., Sakmann, B., Berkovic, S. F., Sprengel, R., & Petrou, S.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2007-10-30
- Volume
- 104
- Issue
- 44
- Pages
- 17536-17541
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2152230432
- Cited by
- 215
- References
- 5
- FWCI
- 7.83
- Type
- journal article
- Language
- en
- Open access
- green
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- Tan, H. O., Reid, C. A., Single, F. N., Davies, P. J., Chiu, C., Murphy, S., Clarke, A. L., Dibbens, L., Krestel, H., Mulley, J. C., Jones, M. V., Seeburg, P. H., Sakmann, B., Berkovic, S. F., Sprengel, R., & Petrou, S. (2007). Reduced cortical inhibition in a mouse model of familial childhood absence epilepsy. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0708440104
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
