Functional studies of a Stx1b knock-out mouse model associated with febrile seizures

Abstract

Epilepsy is one of the most common neurological diseases worldwide. Patients with epilepsy manifest with different kinds of symptoms, such as disturbances of sensation, abnormal involuntary movements, or cognitive functions. However, the mechanisms triggering epilepsy are yet unclear. Increasing evidence from recent studies indicates that genetic factors play an essential role in this disease, including variants in STX1B. In this project, I investigated the functional consequences of haploinsufficiency of Stx1b in a heterozygote Stx1b knock-out mouse model. The whole-cell patch-clamp technique was applied to cultured hippocampal neurons and interneurons from brain slices to examine excitatory and inhibitory synaptic activity. The statistical analysis shows no significant difference in frequencies and amplitudes of mIPSCs and mEPSCs obtained from this part of experiments between Stx1b +/- and WT mice. MEA recordings were further performed to record neuronal activity under hyperthermia. Neuronal activity in slices from both Stx1b+/- and WT mice was significantly enhanced under hyperthermia, but the increase in activity was significantly more pronounced in Stx1b+/- compared to WT mice. It indicates that the haploinsufficiency of Stx1b plays an important role in hyperthermia-evoked neuronal activity, which may explain the clinical observation of febrile seizures observed in patients carrying nonsense mutations.