Tsutomu Hashikawa

RIKEN | RIKEN AICS · Brain Science Institute (BSI)

SLITRK2 encodes a transmembrane protein that modulates neurite outgrowth and synaptic activities and is implicated in bipolar disorder. Here, we addressed its physiological roles in mice. In the brain, the Slitrk2 protein was strongly detected in the hippocampus, vestibulocerebellum, and precerebellar nuclei—the vestibular-cerebellar-brainstem neur...

In a recent review, we have suggested a neuroinvasive potential of SARS‐CoV‐2 and its possible role in the causation of acute respiratory failure of COVID‐19 patients (J Med Viol doi: 10.1002/jmv.25728), based upon the clinical and experimental data available on the past SARS‐CoV‐1 and the recent SARS‐CoV‐2 pandemic. In this article, we provide new...

Following the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), another highly pathogenic coronavirus named SARS-CoV-2 (previously known as 2019-nCoV) emerged in December 2019 in Wuhan, China, and rapidly spreads around the world. This virus shares highly homological sequence with...

Hippocampal mossy fibers (MFs) project from dentate gyrus granule cells onto the CA2-CA3 region. MF-mediated synaptic transmission plays an important role in hippocampal learning and memory. However, the molecular mechanisms underlying MF synaptic development and subsequent functional organization are not fully understood. We previously reported th...

We present a new 3D digital brain atlas of the non-human primate, common marmoset monkey (Callithrix jacchus), with MRI and coregistered Nissl histology data. To the best of our knowledge this is the first comprehensive digital 3D brain atlas of the common marmoset having normalized multi-modal data, cortical and sub-cortical segmentation, and in a...

Degu (Octodon degus), a rodent native to the Andes Mountains in South America, is commonly known as the trumpet-tailed rat and belongs to the parvorder Caviomorpha along with the chinchilla and guinea pig. As experimental animal models, degus contribute to a variety of medical research fields, for example, those pertaining to diabetes, hyperglycemi...

In the plates, Nissl images with (a) or without (a′) structural demarcations and their corresponding MR images (b) are indicated. Reading methods are similar to those in Chap. 2, showing a slicing level by the line on dorsal view of the brain image, stereotaxic coordinates with Horsley-Clarke’s horizontal zero plane, distance from the midline, and...

In each plate, Nissl sections with structural demarcations (a) and their corresponding MR images (b) are indicated. Reading methods are similar to those in Chap. 2, showing slicing level by the vertical line on lateral view of the brain image, stereotaxic coordinates with Horsley-Clarke’s horizontal zero plane, distance from the interaural level 0...

These are examples of freely cut slices independent from the stereotaxic coordinates but available for the very purpose of slicing.

We present a new 3D digital brain atlas of the non-human primate, common marmoset monkey ( Callithrix jacchus ), with MRI and coregistered Nissl histology data. To the best of our knowledge this is the first comprehensive digital 3D brain atlas of the common marmoset having normalized multi-modal data, cortical and sub-cortical segmentation, and in...

Very-KIND/Kndc1/KIAA1768 (v-KIND) is a brain-specific Ras guanine nucleotide exchange factor carrying two sets of the kinase non-catalytic C-lobe domain (KIND), and is predominantly expressed in cerebellar granule cells. Here, we report the impact of v-KIND deficiency on dendritic and synaptic growth in cerebellar granule cells in v-KIND knockout (...

Rotarod performance test. (TIF)

Materials and methods. (DOCX)

vGluT2-immunoreactivity in whole cerebellar sections of wild-type and v-KIND KO mice. (TIF)

GABAAR-α6 immunoreactivity in cerebellar lobules IV–V of wild-type and v-KIND KO mice. (TIF)

Summary of behavioral tests concerning memory, cognition, emotion and nociception. (DOCX)

Opalin, a central nervous system-specific myelin protein phylogenetically unique to mammals, has been suggested to play a role in mammalian-specific myelin. To elucidate the role of Opalin in mammalian myelin, we disrupted the Opalin gene in mice and analyzed the impacts on myelination and behavior. Opalin-knockout (Opalin−/−) mice were born at a M...

Quantitative analysis of western blots suggests no significant change in MBP bands (1–4) between Opalin−/− and Opalin+/+ mice at 3–8 weeks. Myelin proteins from three mice (N = 3) for both genotypes were analyzed by western blotting with anti-MBP antibody. Signal intensities of MBP bands were analyzed with ImageJ. Bars represent means ± SEM for ban...

FUS/TLS is an RNA-binding protein whose genetic mutations or pathological inclusions are associated with neurological diseases including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration, and essential tremor (ET). It is unclear whether their pathogenesis is mediated by gain or loss of function of FUS/TLS. Here, we established...

Since the availability of the common marmoset monkey as a primate model in neuroscience research has recently increased, much effort has been made to develop a reliable guide of the brain structures of this species. In this article, we review the development of the marmoset brain atlas and discuss a newly developed brain model, which was reconstruc...

INCF Japan Node (J-Node) has developed 13 neuroinformatics platforms on topics of vision science, BMI, invertebrate brain, cerebellum function, neuro-imaging, cerebellar transcription, dynamical brain, comprehensive brain science, mouse phenotype, on-line simulation, brain science dictionary, transcriptome brain tomography and RIKEN BSI data and to...

Synaptic cell adhesion molecules are increasingly gaining attention for conferring specific properties to individual synapses. Netrin-G1 and netrin-G2 are trans-synaptic adhesion molecules that distribute on distinct axons, and their presence restricts the expression of their cognate receptors, NGL1 and NGL2, respectively, to specific subdendritic...

The inferior olive (IO) sends excitatory inputs to the cerebellar cortex and cerebellar nuclei through the climbing fibers. In eyeblink conditioning, a model of motor learning, the inactivation of or a lesion in the IO impairs the acquisition or expression of conditioned eyeblink responses. Additionally, climbing fibers originating from the IO are...

The microtubule-associated protein tau is a principal component of neurofibrillary tangles, and has been identified as a key molecule in Alzheimer's disease and other tauopathies. However, it is unknown how a protein that is primarily located in axons is involved in a disease that is believed to have a synaptic origin. To investigate a possible syn...

Degus (Octodon degus) are rodents that are becoming more widely used in the neuroscience field. Degus display several more complex behaviors than rats and mice, including complicated social behaviors, vocal communications, and tool usage with superb manual dexterity. However, relatively little information is known about the anatomy of degu brains....

We investigated a unique microzone of the cerebellum located in folium-p (fp) of rabbit flocculus. In fp, Purkinje cells were potently excited by stimulation of the hypothalamus or mesencephalic periaqueductal gray, which induced defense reactions. Using multiple neuroscience techniques, we determined that this excitation was mediated via beaded ax...

The structural maintenance of neural circuits is critical for higher brain functions in adulthood. Although several molecules have been identified as regulators for spine maintenance in hippocampal and cortical neurons, it is poorly understood how Purkinje cell (PC) spines are maintained in the mature cerebellum. Here we show that the calcium chann...

Swine hemagglutinating encephalomyelitis virus (HEV) has been shown to have a capability to propagate via neural circuits to the central nervous system after peripheral inoculation, resulting in acute deadly encephalomyelitis in natural host piglets as well as in experimental younger rodents. This study has systematically examined the assembly and...

Some central nervous system neurons express receptors of gastrointestinal hormones, but their pharmacological actions are not well known. Previous anatomical and unit recording studies suggest that a group of cerebellar Purkinje cells express motilin receptors, and motilin depresses the spike discharges of vestibular nuclear neurons that receive di...

Swine hemagglutinating encephalomyelitis virus (HEV) has been shown to have a capability to gain access to the cell bodies of sensory neurons after peripheral inoculation, resulting in ganglionic infection. It is not clearly understood how this virus is replicated within and released from the sensory neurons, and it remains to know how satellite ce...

Synaptic cell adhesion molecules are increasingly gaining attention for conferring specific properties to individual synapses. Netrin-G1 and netrin-G2 are trans-synaptic adhesion molecules that distribute on distinct axons, and their presence restricts the expression of their cognate receptors, NGL1 and NGL2, respectively, to specific subdendritic...

Summary of Lrrtm1 KO behavioral analysis. (PDF)

Recent genetic linkage analysis has shown that LRRTM1 (Leucine rich repeat transmembrane neuronal 1) is associated with schizophrenia. Here, we characterized Lrrtm1 knockout mice behaviorally and morphologically. Systematic behavioral analysis revealed reduced locomotor activity in the early dark phase, altered behavioral responses to novel environ...

Cyclin-dependent kinase 5 (Cdk5) plays a pivotal role in neuronal migration and differentiation, and in axonal elongation. Although many studies have been conducted to analyze neuronal functions of Cdk5, its kinase activity has also been reported during oligodendrocyte differentiation, which suggests Cdk5 may play an important role in oligodendrocy...

Transduction of Purkinje cells in vivo with AAV-GFP. A: Schematic drawing depicting virus injection site. AAV-GFP was injected in the molecular layer in the area of developing lobules IV–VI with a microsyringe. B: GFP fluorescence in a sagittal section of the cerebellar vermis at P30. AAV-GFP spread to all lobules and preferentially transduced Purk...

Analyses of dendrite remodeling in tracer-labeled Purkinje cells. Sagittal (left) and coronal (right) views of Purkinje cells at P18 (A) and P25 (B) labeled with BDA tracer. Arrows in (B) indicate background staining. The P18 Purkinje cell extends dendrites in multiple sagittal planes, while the P25 Purkinje cell arranges dendrites in a single sagi...

Persistent multiple CF innervation induced by chronic application of harmaline. A: Confocal and graphic images of an AAV-GFP-infected Purkinje cell and CFs in P30 mice treated with harmaline between P9–P14. Triple fluorescence for Purkinje cells (pseudocolored in blue), BDA-labeled CFs (magenta) and vesicular glutamate transporter VGluT2 (green) is...

Dendrite development in early postnatal weeks. Confocal and graphic images of Purkinje cells at P7, P9 and P14. Respective sagittal (left) and coronal (right) views are shown. Remodeling from random, stellate dendrites to flat, oriented dendrites occurs between P7 and P9. Heterotopic dendrites extruded from the main sagittal plane of the stem dendr...

Mono-CF innervation in monoplanar Purkinje cells. A: Confocal images of a monoplanar Purkinje cell (green), CFs (blue), and VGluT2 (magenta) at P25. The main ascending fiber is indicated by arrowheads. Scale bar, 20 µm. B: Graphic images of the CFs and Purkinje cell shown in A. The main ascending CF (yellow) innervates the monoplanar dendrites (whi...

Rotational 3D movie of P9 Purkinje cell. (AVI)

Rotational 3D movie of P22 Purkinje cell. (AVI)

Multiple CF innervation to dendritic arbors in distinct sagittal planes. A: AAV-GFP-infected Purkinje cell (pseudocolored in blue) receiving inputs from multiple CFs (magenta) shown in Fig. 3C. This Purkinje cell extends dendrites in three distinct sagittal planes (white, light and dark blue in graphic images on the right) and receives inputs from...

Rotational 3D movie of P6 Purkinje cell. (AVI)

Rotational 3D movie of P18 Purkinje cell. (AVI)

Dendrite arborization patterns are critical determinants of neuronal connectivity and integration. Planar and highly branched dendrites of the cerebellar Purkinje cell receive specific topographical projections from two major afferent pathways; a single climbing fiber axon from the inferior olive that extend along Purkinje dendrites, and parallel f...

[This corrects the article on p. e1001065 in vol. 7.].

Deranged Ca(2+) signaling and an accumulation of aberrant proteins cause endoplasmic reticulum (ER) stress, which is a hallmark of cell death implicated in many neurodegenerative diseases. However, the underlying mechanisms are elusive. Here, we report that dysfunction of an ER-resident Ca(2+) channel, inositol 1,4,5-trisphosphate receptor (IP(3)R)...

Nuclear volume and the number of nuclear pore complexes (NPCs) on the nucleus almost double during interphase in dividing cells. How these events are coordinated with the cell cycle is poorly understood, particularly in mammalian cells. We report here, based on newly developed techniques for visualizing NPC formation, that cyclin-dependent kinases...

Although actin is known to play important roles in synapses, immunocytochemical and structural studies on synaptic actin have resulted in conflicting data, and the presence and precise localization of filamentous actin (F-actin) in the synapses have still not been well clarified. We recently described a phalloidin-based antifluorescein isothiocyana...

Nuclear pore complexes (NPCs) are 'supramolecular complexes' on the nuclear envelope assembled from multiple copies of approximately 30 different proteins called nucleoporins (Nups) that provide aqueous channels for nucleocytoplasmic transport during interphase. Although the structural aspects of NPCs have been characterized in detail, NPC formatio...

The extracellular matrix (ECM) plays important roles in the development and plasticity of the central nervous system, and it has been shown that it regulates reorganization of the neuronal network. We have found that expression of OCC1, testican-1, testican-2, testican-3, SPARC and SC1 mRNAs, which encode members of the OCC1-related family of ECM p...

The goal of the INCF Digital Atlasing Program is to provide the vision and direction necessary to make the rapidly growing collection of multidimensional data of the rodent brain (images, gene expression, etc.) widely accessible and usable to the international research community. This Digital Brain Atlasing Standards Task Force was formed in May 20...

Mutations of voltage-gated sodium channel alpha(II) gene, SCN2A, have been described in a wide spectrum of epilepsies. While inherited SCN2A mutations have been identified in multiple mild epilepsy cases, a de novo SCN2A-R102X mutation, which we previously reported in a patient with sporadic intractable childhood localization-related epilepsy, rema...

We have previously revealed that occ1 is preferentially expressed in the primary visual area (V1) of the monkey neocortex. In our attempt to identify more area-selective genes in the macaque neocortex, we found that testican-1, an occ1-related gene, and its family members also exhibit characteristic expression patterns along the visual pathway. The...

To study the molecular mechanism how cortical areas are specialized in adult primates, we searched for area-specific genes in macaque monkeys and found striking enrichment of serotonin (5-hydroxytryptamine, 5-HT) 1B receptor mRNA, and to a lesser extent, of 5-HT2A receptor mRNA, in the primary visual area (V1). In situ hybridization analyses reveal...

Inhibitory interneurons in the hippocampus and neocortex are differentiated into several morphological and functional subtypes that innervate distinct subcellular domains of principal neurons. In the olfactory bulb (OB), odor information is processed by local neuronal circuits that include the major inhibitory interneuron, granule cells (GCs). All...

The organization of F-actin in the ventricular system has been reported to display pronounced regional differences with respect to shape, size, and development. However, the real roles played by F-actin in these cells cannot be understood unless the precise localization of F-actin is defined. In the present study, we used double-fluorescence labeli...