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Furuichi, T.

Publications and source records attributed to Furuichi, T..

2 recordsLinked to original sources

Parallelized analysis of spatial gene expression patterns by database integration

We developed a computational framework for automated integration of a large number of two-dimensional (2D) images with three-dimensional (3D) image datasets located in the standard 3D coordinate. We applied the framework to 2,810 para-sagittal sectioned mouse brain 2D images of in situ hybridization (ISH), archived in the BrainTx database (http://www.cdtdb.neuroinf.jp). We registered the ISH images into the mouse standard coordinate space for MR images, Waxholm space (WHS, https://www.nitrc.org/projects/incfwhsmouse) by linearly transforming them into each of a series of para-sagittal MR image slices, and identifying the best-fit slice by calculating the similarity metric value ({delta}). Transformed 2D images were compared with 3D gene expression image datasets, which were made using a microtomy-based microarray assay system, Transcriptome Tomography, and archived in the ViBrism DB (http://vibrism.neuroinf.jp): the 3D images are located in the WHS.\n\nWe first transformed ISH images of 10 regionally expressed genes and compared them to signals of corresponding 3D expression images in ViBrism DB for evaluating the integration schema: two types of data, produced with different modalities and originally located in different dimensions, were successfully compared after enhancing ISH signals against background noise. Then, for the massive transformation of BrainTx database images, we parallelized our framework, using the IPython cluster package, and implemented it on the PC cluster provided for the Brain Atlasing Hackathon activity hosted by Neuroinformatics Japan Center in Japan. We could identify the best-fit positions for all of the ISH images. All programs were made available through the GitHub repository, at the web site of neuroinformatics/bah2016_registration (https://github.com/neuroinformatics/bah2016_registration).

neuroscience

Deletion of class II ARF causes essential tremors through Nav1.6 traffic impairment

ADP-ribosylation factors (ARFs) are a family of small monomeric GTPases consisting of three classes. In the present study, we generated class II ARF-deficient mice (ARF4+/-/ARF5-/-) and found that they exhibited severe movement-associated tremors. Treatment of the mice with propranolol and gabapentin, which alleviate symptoms in patients with essential tremors, similarly reduced the amplitude of the pathologic tremors. In vivo electrophysiological recordings of the ARF4+/-/ARF5-/- mice revealed that they exhibited reduced excitability of their cerebellar Purkinje cells. Immunohistochemical studies revealed that ARF4+/-/ARF5-/- mice exhibit a severe, selective reduction of Nav1.6 proteins that are important for maintaining repetitive action potential firing in the axon initial segments (AISs) of the Purkinje cells. This decrease in Nav1.6 protein expression and the consequent tremors were alleviated by Purkinje cell-specific expression of ARF5. These results indicate that class II ARF mediates the selective trafficking of Nav1.6 to the AISs in cerebellar Purkinje cells, and suggest that the essential tremors can be ascribed to the reduced intrinsic excitability of Purkinje cells, caused by the selective decrease of Nav1.6 proteins in the AISs.

neuroscience