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Sox1-deficient mice suffer from epilepsy associated with abnormal ventral forebrain development and olfactory cortex hyperexcitability

Malas, S., Postlethwaite, M., Ekonomou, A., Whalley, B., Nishiguchi, S., Wood, H., Meldrum, B., Constanti, A. and Episkopou, V. (2003) Sox1-deficient mice suffer from epilepsy associated with abnormal ventral forebrain development and olfactory cortex hyperexcitability. Neuroscience, 119 (2). pp. 421-432. ISSN 0306-4522

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To link to this item DOI: 10.1016/S0306-4522(03)00158-1


Mutations in several classes of embryonically-expressed transcription factor genes are associated with behavioral disorders and epilepsies. However, there is little known about how such genetic and neurodevelopmental defects lead to brain dysfunction. Here we present the characterization of an epilepsy syndrome caused by the absence of the transcription factor SOX1 in mice. In vivo electroencephalographic recordings from SOX1 mutants established a correlation between behavioral changes and cortical output that was consistent with a seizure origin in the limbic forebrain. In vitro intracellular recordings from three major forebrain regions, neocortex, hippocampus and olfactory (piriform) cortex (OC) showed that only the OC exhibits abnormal enhanced synaptic excitability and spontaneous epileptiform discharges. Furthermore, the hyperexcitability of the OC neurons was present in mutants prior to the onset of seizures but was completely absent from both the hippocampus and neocortex of the same animals. The local inhibitory GABAergic neurotransmission remained normal in the OC of SOX1-deficient brains, but there was a severe developmental deficit of OC postsynaptic target neurons, mainly GABAergic projection neurons within the olfactory tubercle and the nucleus accumbens shell. Our data show that SOX1 is essential for ventral telencephalic development and suggest that the neurodevelopmental defect disrupts local neuronal circuits leading to epilepsy in the SOX1-deficient mice

Item Type:Article
Divisions:Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
ID Code:1721
Uncontrolled Keywords:abnormalities Animal Animals Animals,Newborn Brain Comparative Study deficiency Disease Models,Animal DNA-Binding Proteins Electroencephalography Embryo embryology Epilepsy Female Genes genetics growth & development High Mobility Group Proteins Hippocampus In Vitro Lead Male Matched-Pair Analysis Membrane Potentials metabolism methods Mice Mice,Mutant Strains Mutation Neocortex Neural Conduction Neurons Nucleus Accumbens Olfactory Pathways Patch-Clamp Techniques physiopathology Prosencephalon Proteins Seizures Support,Non-U.S.Gov't Synaptic Transmission Syndrome
Additional Information:DA - 20030528, NOT IN FILE, PM:12770556

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