Microcircuit failure in STXBP1 encephalopathy leads to hyperexcitability
Altair Brito dos Santos, Silas D Larsen, Matthijs Verhage, Jakob B Sørensen, Jean-François Perrier · FENS Forum 2024
De novo mutations in STXBP1 are among the most prevalent causes of neurodevelopmental disorders, and lead to haploinsufficiency, cortical hyperexcitability, epilepsy and other symptoms in patients. Given that Munc18-1, the protein encoded bySTXBP1, is essential for excitatory and inhibitory synaptic transmission, it is currently not understood why mutations cause hyperexcitability. We discover that overall inhibition in canonical feedforward microcircuits is defective in a P15-22 mouse model for Stxbp1 haploinsufficiency. Unexpectedly, we find that inhibitory synapses formed by parvalbumin-pos
ePoster · Neuroscience