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Spinocerebellar ataxia 42 (SCA42) is a neurodegenerative disorder recently shown to be caused by c.5144G > A (p.Arg1715His) mutation in CACNA1G, which encodes the T-type voltage-gated calcium channel CaV3.1. Here, we describe a large Japanese family with SCA42. Postmortem pathological examination revealed severe cerebellar degeneration with prominent Purkinje cell loss without ubiquitin accumulation in an SCA42 patient. To determine whether this mutation causes ataxic symptoms and neurodegeneration, we generated knock-in mice harboring c.5168G > A (p.Arg1723His) mutation in Cacna1g, corresponding to the mutation identified in the SCA42 family. Both heterozygous and homozygous mutants developed an ataxic phenotype from the age of 11-20 weeks and showed Purkinje cell loss at 50 weeks old. Degenerative change of Purkinje cells and atrophic thinning of the molecular layer were conspicuous in homozygous knock-in mice. Electrophysiological analysis of Purkinje cells using acute cerebellar slices from young mice showed that the point mutation altered the voltage dependence of CaV3.1 channel activation and reduced the rebound action potentials after hyperpolarization, although it did not significantly affect the basic properties of synaptic transmission onto Purkinje cells. Finally, we revealed that the resonance of membrane potential of neurons in the inferior olivary nucleus was decreased in knock-in mice, which indicates that p.Arg1723His CaV3.1 mutation affects climbing fiber signaling to Purkinje cells. Altogether, our study shows not only that a point mutation in CACNA1G causes an ataxic phenotype and Purkinje cell degeneration in a mouse model, but also that the electrophysiological abnormalities at an early stage of SCA42 precede Purkinje cell loss.
Pubmed ID: 31229688 RIS Download
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NeuroMatic is a collection of Igor Pro functions for analyzing electrophysiological data. By allowing users to organize their data into Sets and Groups, NeuroMatic makes it relatively easy to compute transformations and statistical analyses on their data, including scaling, alignment averaging, baseline subtraction, spike detection, stationarity analysis, rise-time computations, etc. Being open source and modular designed, NeuroMatic also allows users to develop their own analysis functions that can be easily incorporated into NeuroMatic's framework. Note, if you have reached this page in search of a freeware tool for neuronal reconstructions, you are more likely to be interested in Neuromantic, a software package that sounds like NeuroMatic, but is not quite the same. Features of NeuroMatic Include * Sorting, Scaling, Averaging, Interpolation * Max / Min / Mean / Level / Rise Time / FWHM / Slope Measurements * Stability / Stationarity Analysis * Event Detection * Waveform Template Matching * Spike Raster Plots * Interspike-Interval and Peri-Stimulus Time (PST) Histograms * Compact Easy-to-Use Interface * Modular design as a basis for your own procedures * Extra space for your own buttons and controls * Import functions for Axograph and Pclamp data * Automatic macro generation for batch processing Supporting Agencies: MRC, Wellcome Trust Spike, Event, Fit, NClamp, Acquisition, spike train, EPSP, IPSP, IPSC, EPSC
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