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Dravet syndrome (DS) is a neurodevelopmental disorder due to pathogenic variants in SCN1A encoding the Nav1.1 sodium channel subunit, characterized by treatment-resistant epilepsy, temperature-sensitive seizures, developmental delay/intellectual disability with features of autism spectrum disorder, and increased risk of sudden death. Convergent data suggest hippocampal dentate gyrus (DG) pathology in DS (Scn1a+/-) mice. We performed two-photon calcium imaging in brain slice to uncover a profound dysfunction of filtering of perforant path input by DG in young adult Scn1a+/- mice. This was not due to dysfunction of DG parvalbumin inhibitory interneurons (PV-INs), which were only mildly impaired at this timepoint; however, we identified enhanced excitatory input to granule cells, suggesting that circuit dysfunction is due to excessive excitation rather than impaired inhibition. We confirmed that both optogenetic stimulation of entorhinal cortex and selective chemogenetic inhibition of DG PV-INs lowered seizure threshold in vivo in young adult Scn1a+/- mice. Optogenetic activation of PV-INs, on the other hand, normalized evoked responses in granule cells in vitro. These results establish the corticohippocampal circuit as a key locus of pathology in Scn1a+/- mice and suggest that PV-INs retain powerful inhibitory function and may be harnessed as a potential therapeutic approach towards seizure modulation.

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Nonreducing sugars such as sucrose, raffinose, myo-inositol, pinitol and galactinol were separated on a polyamine-bonded polymer gel (NH 2 type) column using acetonitrile-water as mobile phase. Sugars in the eluate were detected by periodate oxidation and the subsequent derivation of guanidine to fluorescent compounds. Detection limits were: sucrose 2.5, D-glucose 2.5 and pinitol 4 ng. This highly sensitive method was more accurate and rapid for determining sugar contents in immature soybean seeds, sweet corn kernels and chinese mustard leaves than the conventional method using refractive index detection. Also, this method reduced the injection volumes of extracts to the column and allowed to lengthen the column life.