Neuroscience and Behavior

Introduction: To compare mifepristone alone to osmotic dilators with mifepristone and to osmotic dilators with placebo for cervical preparation for surgical abortion after 19 weeks' gestation. All groups received preprocedure misoprostol. Methods: We conducted a site-stratified, double-blinded randomized controlled trial of women undergoing dilation and evacuation (D&E) at 19-23 6/7 weeks' gestation randomized to one of three groups: (1) mifepristone

Developmental and Epileptic Encephalopathies (DEEs), a class of devastating neurological disorders characterized by recurrent seizures and exacerbated by disruptions to excitatory/inhibitory balance in the brain, are commonly caused by mutations in ion channels. Disruption of, or variants in, FGF13 were implicated as causal for a set of DEEs, but the underlying mechanisms were clouded because FGF13 is expressed in both excitatory and inhibitory neurons, FGF13 undergoes extensive alternative splicing producing multiple isoforms with distinct functions, and the overall roles of FGF13 in neurons are incompletely cataloged. To overcome these challenges, we generated a set of novel cell type-specific conditional knockout mice. Interneuron-targeted deletion of Fgf13 led to perinatal mortality associated with extensive seizures and impaired the hippocampal inhibitory/excitatory balance while excitatory neuron-targeted deletion of Fgf13 caused no detectable seizures and no survival deficits. While best studied as a voltage-gated sodium channel (Nav) regulator, we observed no effect of Fgf13 ablation in interneurons on Navs but rather a marked reduction in K + channel currents. Re-expressing different Fgf13 splice isoforms could partially rescue deficits in interneuron excitability and restore K + channel current amplitude. These results enhance our understanding of the molecular mechanisms that drive the pathogenesis of Fgf13-related seizures and expand our understanding of FGF13 functions in different neuron subsets. .

SummaryThe canonical G406R gain of function mutation that reduces inactivation and increases Ca2+influx through theCACNA1C-encoded CaV1.2 voltage gated Ca2+channel underlies the multisystem disorder Timothy syndrome (TS), characterized by invariant Long QT syndrome and consequent life-threatening arrhythmias. Severe episodic hypoglycemia, which exacerbates arrhythmia risk, is among the myriad non-cardiac TS pathologies that are poorly characterized. While hypoglycemia is thought to result from increased Ca2+influx through CaV1.2 channels in pancreatic beta cells and consequent hyperinsulinism, this mechanism has never been demonstrated due to a lack of informative animal models, thus hampering development of preventive strategies. We generated a CaV1.2 G406R knockin mouse model that recapitulates key TS features including hypoglycemia. Unexpectedly, these mice did not show hyperactive beta cells or hyperinsulinism in the setting of normal intrinsic beta cell function, suggesting dys...

ABSTRACTBackgroundCortical demyelinated lesions are prevalent in multiple sclerosis (MS) and associated with disability; their presence on MRI has recently been incorporated into MS diagnostic criteria. Presently, advanced and ultra-high-field MRI — not routinely available in clinical practice — are the most sensitive methods for detection of cortical lesions, and approaches utilizing MRI sequences obtainable in routine clinical practice remain an unmet need.ObjectiveTo assess the sensitivity of the ratio of T1-weighted and T2-weighted (T1/T2) signal intensity for focal cortical lesions in comparison to other established, sensitive, advanced and high-field imaging methods.Methods3-tesla (3T) and 7-tesla (7T) MRI collected from 10 adults with MS participating in a natural history study at the National Institutes of Health were included in the study. T1/T2 images were calculated by dividing 3T T1w images by 3T T2w fluid-attenuated inversion recovery (FLAIR) images for each participant...