Behavioral Comorbidities and Drug Treatments in a Zebrafish scn1lab Model of Dravet Syndrome.

Loss-of-function mutations in SCN1A cause Dravet syndrome (DS), a catastrophic childhood epilepsy in which patients experience comorbid behavioral conditions, including movement disorders, sleep abnormalities, anxiety, and intellectual disability. To study the functional consequences of voltage-gated sodium channel mutations, we use zebrafish with a loss-of-function mutation in scn1lab, a zebrafish homolog of human SCN1A. Homozygous scn1labs552/s552 mutants exhibit early-life seizures, metabolic deficits, and early death. Here, we developed in vivo assays using scn1labs552 mutants between 3 and 6 d postfertilization (dpf). To evaluate sleep disturbances, we monitored larvae for 24 h with locomotion tracking software. Locomotor activity during dark (night phase) was significantly higher in mutants than in controls. Among anticonvulsant drugs, clemizole and diazepam, but not trazodone or valproic acid, decreased distance moved at night for scn1labs552 mutant larvae. To monitor exploratory behavior in an open field, we tracked larvae in a novel arena. Mutant larvae exhibited impaired exploratory behavior, with increased time spent near the edge of the arena and decreased mobility, suggesting greater anxiety. Both clemizole and diazepam, but not trazodone or valproic acid, decreased distance moved and increased time spent in the center of the arena. Counting inhibitory neurons in vivo revealed no differences between scn1labs552 mutants and siblings. Taken together, our results demonstrate conserved features of sleep, anxiety, and movement disorders in scn1lab mutant zebrafish, and provide evidence that a zebrafish model allows effective tests of treatments for behavioral comorbidities associated with DS

On the Integrability, B\"Acklund Transformation and Symmetry Aspects of a Generalized Fisher Type Nonlinear Reaction-Diffusion Equation

The dynamics of nonlinear reaction-diffusion systems is dominated by the onset of patterns and Fisher equation is considered to be a prototype of such diffusive equations. Here we investigate the integrability properties of a generalized Fisher equation in both (1+1) and (2+1) dimensions. A Painlev\'e singularity structure analysis singles out a special case ($m=2$) as integrable. More interestingly, a B\"acklund transformation is shown to give rise to a linearizing transformation for the integrable case. A Lie symmetry analysis again separates out the same $m=2$ case as the integrable one and hence we report several physically interesting solutions via similarity reductions. Thus we give a group theoretical interpretation for the system under study. Explicit and numerical solutions for specific cases of nonintegrable systems are also given. In particular, the system is found to exhibit different types of travelling wave solutions and patterns, static structures and localized structures. Besides the Lie symmetry analysis, nonclassical and generalized conditional symmetry analysis are also carried out.Comment: 30 pages, 10 figures, to appear in Int. J. Bifur. Chaos (2004