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Significance Smith–Magenis syndrome (SMS) is a neurodevelopmental disorder associated with autism and epileptic seizures. SMS is caused by losing one copy of the gene encoding retinoic acid induced 1 (RAI1),… Click to show full abstract
Significance Smith–Magenis syndrome (SMS) is a neurodevelopmental disorder associated with autism and epileptic seizures. SMS is caused by losing one copy of the gene encoding retinoic acid induced 1 (RAI1), a ubiquitously expressed transcriptional regulator. To pinpoint brain regions and cell types contributing to neuronal hyperexcitability in SMS, we combined electrophysiology and three-dimensional imaging of Fos expression in the intact mouse brain. We found that Rai1-deficient hippocampal dentate gyrus granule cells (dGCs) show increased intrinsic excitability and enhanced glutamatergic synaptic transmission. Our findings indicate that Rai1 safeguards the hippocampal network from hyperexcitability and could help explain abnormal brain activity in SMS.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2022
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