Topic: Munc18-1

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

De novo mutations in STXBP1 are among the most prevalent causes of neurodevelopmental disorders, leading to haploinsufficiency, cortical hyperexcitability, epilepsy, and motor impairments. STXBP1 encodes for Munc18-1, an essential protein for synaptic transmission. In a mouse model of the disease, we found that excitatory synapses, not inhibitory synapses, are impaired during early stages of the disease. Consequently, excitatory synapses fail to recruit parvalbumin-positive (PV) inhibitory interneurons in feedforward inhibitory microcircuits, leading to cortical hyperexcitability. In this stud

Establishing synaptic connections between neurons is essential for neuronal circuitry and efficient brain communication While the role of neuronal activity in refining and maintaining synapses is well known, we focus on its role, specifically spontaneous neurotransmitter release, for synapse formation between dentate gyrus axons, the mossy fibres (MF), onto CA3 pyramidal cells in the hippocampus. Neurotransmitter release occurs through two primary modes: action potential induced release and spontaneous fusion of synaptic vesicles. These modes are underpinned by distinct pools of vesicles, exhi