Graduate University for Advanced Studies
Tokyo, Japan

The Graduate University for Advanced Studies is one of the national universities of Japan, located in the town of Hayama in Kanagawa Prefecture. Sōkendai , as it is generally called in its abbreviated form, was established in the year 1988. From 1988 to 1995 the university maintained its headquarters in Nagatsuta, Midori-ku, Yokohama at Tokyo Institute of Technology later shifting to the present location. Wikipedia.

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Tachibana Y.,U.S. National Institutes of Health | Tachibana Y.,Graduate University for Advanced Studies | Hikosaka O.,U.S. National Institutes of Health
Neuron | Year: 2012

Motor actions are facilitated when expected reward value is high. It is hypothesized that there are neurons that encode expected reward values to modulate impending actions and potentially represent motivation signals. Here, we present evidence suggesting that the ventral pallidum (VP) may participate in this process. We recorded single neuronal activity in the monkey VP using a saccade task with a direction-dependent reward bias. Depending on the amount of the expected reward, VP neurons increased or decreased their activity tonically until the reward was delivered, for both ipsiversive and contraversive saccades. Changes in expected reward values were also associated with changes in saccade performance (latency and velocity). Furthermore, bilateral muscimol-induced inactivation of the VP abolished the reward-dependent changes in saccade latencies. These data suggest that the VP provides expected reward value signals that are used to facilitate or inhibit motor actions.

Chiken S.,Graduate University for Advanced Studies | Nambu A.,Graduate University for Advanced Studies
Journal of Neuroscience | Year: 2013

To elucidate the mechanism of deep brain stimulation (DBS) targeting the internal segment of the globus pallidus (GPi), neuronal activity of the GPi and the external segment of the globus pallidus (GPe) was examined during local electrical microstimulation in normal awake monkeys. Single-pulse stimulation of the GPi evoked brief inhibition in neighboring GPi neurons, which was mediated by GABAA receptors. High-frequency stimulation of the GPi completely inhibited spontaneous firings of GPi neurons by activation of GABAA and GABAB receptors. Local single-pulse stimulation directly excited some GPi neurons. Such directly evoked responses were also inhibited by high-frequency stimulation through GABAA receptors. In contrast to the GPi, single-pulse and high-frequency stimulation of the GPe induced complex responses composed of GABAergic inhibition and glutamatergic excitation in neighboring GPe neurons. Cortically evoked triphasic responses of GPi neurons were completely inhibited during high-frequency GPi stimulation. These findings suggest that GPi-DBS dissociates inputs and outputs in the GPi by intense GABAergic inhibition and disrupts information flow through the GPi. © 2013 the authors.

Chiken S.,Graduate University for Advanced Studies | Nambu A.,Graduate University for Advanced Studies
Frontiers in Systems Neuroscience | Year: 2014

Applying high-frequency stimulation (HFS) to deep brain structure, known as deep brain stimulation (DBS), has now been recognized an effective therapeutic option for a wide range of neurological and psychiatric disorders. DBS targeting the basal ganglia thalamo-cortical loop, especially the internal segment of the globus pallidus (GPi), subthalamic nucleus (STN) and thalamus, has been widely employed as a successful surgical therapy for movement disorders, such as Parkinson's disease, dystonia and tremor. However, the neurophysiological mechanism underling the action of DBS remains unclear and is still under debate: does DBS inhibit or excite local neuronal elements? In this review, we will examine this question and propose the alternative interpretation: DBS dissociates inputs and outputs, resulting in disruption of abnormal signal transmission. © 2014. Chiken and Nambu.

Otsuka T.,Graduate University for Advanced Studies | Kawaguchi Y.,Japan Science and Technology Agency
Journal of Neuroscience | Year: 2011

Recent advances have established that intralaminar and interlaminar excitatory networks between neocortical pyramidal cells are specialized into subnetworks. Here, we have investigated how the commissural system organizes the intracortical excitatory subnetworks to communicate between cortical hemispheres. Whole-cell recordings were obtained from callosal projection neurons [commissural (COM) cells], identified by in vivo injection of retrograde fluorescent tracer into one hemisphere, in rat frontal cortical slices. We found that layer V (L5) COM cells were heterogeneous in physiological and morphological properties that correlated with projection patterns to contralateral and ipsilateral cortical areas. The probability of synaptically connected pairs of L5 COM cells was higher in cell pairs of the same firing subtypes than that in different cell subtype pairs. In interlaminar connections, layer II/III (L2/3) COM cells preferentially innervated L5 COM cells. Moreover, pairs of the same L5 COM subtypes were more likely to share inputs from L2/3 COM cells than were different COM subtype cell pairs. In addition, common inputs from L2/3 COM cells were frequently observed in L5 pairs of corticopontine cells and given firing subtypes of COM cells. Our results suggest that callosal communications are achieved via several distinct COM cell subnetworks differentiated according to the ipsilateral corticocortical and subcortical projection patterns. Copyright © 2011 the authors.

Yamamori T.,Graduate University for Advanced Studies
Progress in Neurobiology | Year: 2011

The neocortex, which is characteristic of mammals, has evolved to play important roles in cognitive and perceptual functions. The localization of different functions in different regions of the neocortex was well established within the last century. Studies on the formation of the neocortex have advanced at the molecular level, thus clarifying the mechanisms that control neural or glial cell differentiation and sensory projections. However, mechanisms that underlie cortical area specialization remain unsolved. To address this problem, our approach has been to isolate and characterize the genes that are selectively expressed in particular subsets of neocortical areas in primates; these areas are most distinctive among mammals. By differential display and restriction landmark cDNA scanning (RLCS) methods, we have identified two major classes of genes that are specifically expressed in the adult macaque monkey neocortical areas: one is expressed in the primary sensory areas, particularly, in the primary visual cortex (V1) and the other is expressed in the association areas. The genes that show these specific expression patterns are limited to only several gene families among our large-scale screening. In this review, I first describe the isolation and characterization of these genes, along with another class of genes specifically expressed in motor areas. Then, I discuss their functional significance in the primate neocortex. Finally, I discuss the implication of these gene expression patterns in neocortical specialization in primates and possible future research directions. © 2011 Elsevier Ltd.

Fukagawa T.,Graduate University for Advanced Studies | Earnshaw W.C.,University of Edinburgh
Developmental Cell | Year: 2014

Since discovery of the centromere-specific histone H3 variant CENP-A, centromeres have come to be defined as chromatin structures that establish the assembly site for the complex kinetochore machinery. In most organisms, centromere activity is defined epigenetically, rather than by specific DNA sequences. In this review, we describe selected classic work and recent progress in studies of centromeric chromatin with a focus on vertebrates. We consider possible roles for repetitive DNA sequences found at most centromeres, chromatin factors and modifications that assemble and activate CENP-A chromatin for kinetochore assembly, plus the use of artificial chromosomes and kinetochores to study centromere function. © 2014 The Authors.

Kondo S.,Graduate University for Advanced Studies | Ueda R.,Graduate University for Advanced Studies
Genetics | Year: 2013

We report a simple yet extremely efficient platform for systematic gene targeting by the RNA-guided endonuclease Cas9 in Drosophila. The system comprises two transgenic strains: one expressing Cas9 protein from the germline-specific nanos promoter and the other ubiquitously expressing a custom guide RNA (gRNA) that targets a unique site in the genome. The two strains are crossed to form an active Cas9-gRNA complex specifically in germ cells, which cleaves and mutates the target site. We demonstrate rapid generation of mutants in seven neuropeptide and two microRNA genes in which no mutants have been described. Founder animals stably expressing Cas9-gRNA transmitted germline mutations to an average of 60% of their progeny, a dramatic improvement in efficiency over the previous methods based on transient Cas9 expression. Simultaneous cleavage of two sites by co-expression of two gRNAs efficiently induced internal deletion with frequencies of 4.3-23%. Our method is readily scalable to high-throughput gene targeting, thereby accelerating comprehensive functional annotation of the Drosophila genome. © 2013 by the Genetics Society of America.

Kobayashi T.,Graduate University for Advanced Studies
Proceedings of the Japan Academy Series B: Physical and Biological Sciences | Year: 2014

The ribosomal RNA gene (rDNA) repeats form a historically well-researched region in the chromosome. Their highly repetitive structure can be identified easily which has enabled studies on DNA replication, recombination, and transcription. The region is one of the most unstable regions in the genome because of deleterious recombination among the repeats. The ribosomal RNA gene repeats use a unique gene amplification system to restore the copy number after this has been reduced due to recombination. It has been shown that unstable features in the genome can accelerate cellular senescence that restricts the lifespan of a cell. Here, I will introduce a study by our group that shows how the stability of rDNA is maintained and affects lifespan. I propose that the ribosomal RNA gene repeats constitute a center from which the stability of the whole genome is regulated and the lifespan of the cell is controlled. © 2014 The Japan Academy.

Kobayashi T.,Graduate University for Advanced Studies
Cellular and Molecular Life Sciences | Year: 2011

The genes encoding ribosomal RNA (rRNA) are the most abundant genes in the eukaryotic genome. They reside in tandem repetitive clusters, in some cases totaling hundreds of copies. Due to their repetitive structure and highly active transcription, the rRNA gene repeats are some of the most fragile sites in the chromosome. A unique gene amplification system compensates for loss of copies, thus maintaining copy number, albeit with some fluctuations. The unusual nature of rRNA gene repeats affects cellular functions such as senescence. In addition, we recently found that the repeat number determines sensitivity to DNA damage. In this review, I would like to introduce a new aspect of the rRNA gene repeat (called rDNA) as a center of maintenance of genome integrity and discuss its contribution to evolution. © 2010 The Author(s).

Muratsugu S.,Graduate University for Advanced Studies | Tada M.,Graduate University for Advanced Studies
Accounts of Chemical Research | Year: 2013

Selective catalysis is critical for the development of green chemical processes, and natural enzymes that possess specialized three-dimensional reaction pockets with catalytically active sites represent the most sophisticated systems for selective catalysis. A reaction space in an enzyme consists of an active metal center, functional groups for molecular recognition (such as amino acids), and a surrounding protein matrix to prepare the reaction pocket. The artificial design of such an integrated catalytic unit in a non-enzymatic system remains challenging. Molecular imprinting of a supported metal complex provides a promising approach for shape-selective catalysis. In this process, an imprinted cavity with a shape matched to a template molecule is created in a polymer matrix with a catalytically active metal site.In this Account, we review our studies on molecularly imprinted metal complex catalysts, focusing on Ru complexes, on oxide surfaces for shape-selective catalysis. Oxide surface-attached transition metal complex catalysts not only improve thermal stability and catalyst dispersion but also provide unique catalytic performance not observed in homogeneous precursors. We designed molecularly imprinted Ru complexes by using surface-attached Ru complexes with template ligands and inorganic/organic surface matrix overlayers to control the chemical environment around the active metal complex catalysts on oxide surfaces. We prepared the designed, molecularly imprinted Ru complexes on SiO2 surfaces in a step-by-step manner and characterized them with solid-state (SS) NMR, diffuse-reflectance (DR) UV-vis, X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller isotherm (BET), X-ray fluorescence (XRF), and Ru K-edge extended X-ray absorption fine structure (EXAFS). The catalytic performances of these Ru complexes suggest that this process of molecular imprinting facilitates the artificial integration of catalytic functions at surfaces. Further advances such as the imprinting of a transition state structure or the addition of multiple binding sites could lead to systems that can achieve 100% selective catalysis. © 2012 American Chemical Society.

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