查看文章

Background: Ohtahara syndrome, also known as Early Infantile Epileptic Encephalopathy (EIEE) type 4 with suppression bursts is a currently untreatable disorder that presents with seizures and impaired cognition. EIEE patients have most frequently mutations in the gene encoding the synaptic protein, munc18-1. The exact molecular mechanism is unknown how these munc18-1 mutations cause seizures and cognitive impairment but the leading haploinsufficiency hypothesis posits that they make the protein unstable. This study aims to understand the role of munc18-1 in synaptic transmission, how its point mutations lead to seizures. Methods: Spatial learning of stxbp1 heterozygous mice was evaluated in radial arm maze and synaptic and network effects of stxbp1 mutants were tested using electrophysiology and fluorescence imaging.

Results: This study showed that haploinsufficiency of stxbp1 results in mild …