National Institute for Physiological science

Okazaki, Japan

National Institute for Physiological science

Okazaki, Japan
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Sasaki T.,National Institute for Physiological science
Neuroscience Research | Year: 2013

In the mammalian cortex, axons are highly ramified and link an enormous number of neurons over large distances. The conventional view assumes that action potentials (APs) are initiated at the axon initial segment in an all-or-none fashion and are then self-propagated orthodromically along axon collaterals without distortion of the AP waveform. By contrast, recent experimental results suggest that the axonal AP waveform can be modified depending on the activation states of the ion channels and receptors on axonal cell membranes. This AP modulation can regulate neurotransmission to postsynaptic neurons. In addition, the latest studies have provided evidence that cortical axons can integrate somatic burst firings and promote activity-dependent ectopic AP generation, which may underlie the oscillogenesis of fast rhythmic network activity. These seminal observations indicate that axons can perform diverse functional operations that extend beyond the prevailing model of axon physiology. © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society.


Sasaki T.,National Institute for Physiological science
Proceedings of the National Academy of Sciences of the United States of America | Year: 2012

Dynamic activity of glia has repeatedly been demonstrated, but if such activity is independent from neuronal activity, glia would not have any role in the information processing in the brain or in the generation of animal behavior. Evidence for neurons communicating with glia is solid, but the signaling pathway leading back from glial-to-neuronal activity was often difficult to study. Here, we introduced a transgenic mouse line in which channelrhodopsin-2, a light-gated cation channel, was expressed in astrocytes. Selective photostimulation of these astrocytes in vivo triggered neuronal activation. Using slice preparations, we show that glial photostimulation leads to release of glutamate, which was sufficient to activate AMPA receptors on Purkinje cells and to induce long-term depression of parallel fiber-to-Purkinje cell synapses through activation of metabotropic glutamate receptors. In contrast to neuronal synaptic vesicular release, glial activation likely causes preferential activation of extrasynaptic receptors that appose glial membrane. Finally, we show that neuronal activation by glial stimulation can lead to perturbation of cerebellar modulated motor behavior. These findings demonstrate that glia can modulate the tone of neuronal activity and behavior. This animal model is expected to be a potentially powerful approach to study the role of glia in brain function.


Fukata Y.,National Institute for Physiological science | Fukata Y.,Japan Science and Technology Agency | Fukata M.,National Institute for Physiological science
Nature Reviews Neuroscience | Year: 2010

Protein palmitoylation, a classical and common lipid modification, regulates diverse aspects of neuronal protein trafficking and function. The reversible nature of palmitoylation provides a potential general mechanism for protein shuttling between intracellular compartments. The recent discovery of palmitoylating enzymes a large DHHC (Asp-His-His-Cys) protein family and the development of new proteomic and imaging methods have accelerated palmitoylation analysis. It is becoming clear that individual DHHC enzymes generate and maintain the specialized compartmentalization of substrates in polarized neurons. Here, we discuss the regulatory mechanisms for dynamic protein palmitoylation and the emerging roles of protein palmitoylation in various aspects of pathophysiology, including neuronal development and synaptic plasticity. © 2010 Macmillan Publishers Limited. All rights reserved.


Alstermark B.,Umeå University | Isa T.,National Institute for Physiological science
Annual Review of Neuroscience | Year: 2012

From an evolutionary perspective, it is clear that basic motor functions such as locomotion and posture are largely controlled by neural circuitries residing in the spinal cord and brain-stem. The control of voluntary movements such as skillful reaching and grasping is generally considered to be governed by neural circuitries in the motor cortex that connect directly to motoneurons via the corticomotoneuronal (CM) pathway. The CM pathway may act together with several brainstem systems that also act directly with motoneurons. This simple view was challenged by work in the cat, which lacks the direct CM system, showing that the motor commands for reaching and grasping could be mediated via spinal interneurons with input from the motor-cortex and brain-stem systems. It was further demonstrated that the spinal interneurons mediating the descending commands for reaching and grasping constitute separate and distinct populations from those involved in locomotion and posture. The aim of this review is to describe populations of spinal interneurons that are involved in the control of skilled reaching and grasping in the cat, monkey, and human. © 2012 by Annual Reviews. All rights reserved.


Wasaka T.,National Institute for Physiological science | Kakigi R.,National Institute for Physiological science
NeuroImage | Year: 2012

The role of sensory information in motor control has been studied, but the cortical processing underlying cross-modal relationship between visual and somatosensory information for movement execution remains a matter of debate. Visual estimates of limb positions are congruent with proprioceptive estimates under normal visual conditions, but a mismatch between the watched and felt movement of the hand disrupts motor execution. We investigated whether activation in somatosensory areas was affected by the discordance between the intended and an executed action. Subjects performed self-paced thumb movement of the left hand under normal visual and mirror conditions. The Mirror condition provided a non-veridical and unexpected visual feedback. The results showed activity in the primary somatosensory area to be inhibited and activity in the secondary somatosensory area (SII) to be enhanced with voluntary movement, and neural responses in the SII and parietal cortex were strongly affected by the unexpected visual feedback. These results provide evidence that the visual information plays a crucial role in activation in somatosensory areas during motor execution. A mechanism that monitors sensory inputs and motor outputs congruent with current intension is necessary to control voluntary movement. © 2011.


Obata K.,National Institute for Physiological science
Proceedings of the Japan Academy Series B: Physical and Biological Sciences | Year: 2013

Signal transmission through synapses connecting two neurons is mediated by release of neurotransmitter from the presynaptic axon terminals and activation of its receptor at the postsynaptic neurons. γ-Aminobutyric acid (GABA), non-protein amino acid formed by decarboxylation of glutamic acid, is a principal neurotransmitter at inhibitory synapses of vertebrate and invertebrate nervous system. On one hand glutamic acid serves as a principal excitatory neurotransmitter. This article reviews GABA researches on; (1) synaptic inhibition by membrane hyperpolarization, (2) exclusive localization in inhibitory neurons, (3) release from inhibitory neurons, (4) excitatory action at developmental stage, (5) phenotype of GABA-deficient mouse produced by gene-targeting, (6) developmental adjustment of neural network and (7) neurological/psychiatric disorder. In the end, GABA functions in simple nervous system and plants, and non-amino acid neurotransmitters were supplemented. © 2013 The Japan Academy.


Takao K.,National Institute for Physiological science | Takao K.,Japan Science and Technology Agency | Miyakawa T.,National Institute for Physiological science | Miyakawa T.,Japan Science and Technology Agency | Miyakawa T.,Health Science University
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

The use of mice as animal models has long been considered essential in modern biomedical research, but the role of mouse models in research was challenged by a recent report that genomic responses in mouse models poorly mimic human inflammatory diseases. Here we reevaluated the same gene expression datasets used in the previous study by focusing on genes whose expression levels were significantly changed in both humans and mice. Contrary to the previous findings, the gene expression levels in the mouse models showed extraordinarily significant correlations with those of the human conditions (Spearman's rank correlation coefficient: 0.43-0.68; genes changed in the same direction: 77-93%; P = 6.5 × 10-11 to 1.2 × 10-35). Moreover, meta-analysis of those datasets revealed a number of pathways/biogroups commonly regulated by multiple conditions in humans and mice. These findings demonstrate that gene expression patterns in mouse models closely recapitulate those in human inflammatory conditions and strongly argue for the utility of mice as animal models of human disorders.


Nambu A.,National Institute for Physiological science
Frontiers in Neuroanatomy | Year: 2011

Somatotopic organization is a fundamental and key concept to understand how the corticobasal ganglia loop works. It is also indispensable knowledge to perform stereotaxic surgery for movement disorders. Here I would like to describe the somatotopic organization of the basal ganglia, which consist of the striatum, subthalamic nucleus, globus pallidus, and substantia nigra. Projections from motor cortical regions representing different body parts terminate in different regions of these nuclei. Basal ganglia neurons respond not only to the stimulation of the corresponding regions of the motor cortices, but also to active and passive movements of the corresponding body parts. On the basis of these anatomical and physiological findings, somatotopic organization can be identified in the motor territories of these nuclei in the basal ganglia. In addition, projections from functionally interrelated cortical areas partially converge through the cortico-basal ganglia loop, but nevertheless the somatotopy is still preserved. Disorganized somatotopy may explain, at least in part, the pathophysiology of movement disorders, such as Parkinson's disease and dystonia. © 2011 Nambu.


Kubota Y.,National Institute for Physiological science | Kubota Y.,Graduate University for Advanced Studies | Kubota Y.,Japan Science and Technology Agency
Current Opinion in Neurobiology | Year: 2014

The cerebral cortical microcircuit is composed of pyramidal and non-pyramidal cells and subcortical and cortico-cortical afferents. These constitute a complex wiring structure that remains poorly understood. At least ten non-pyramidal cell subtypes are known. These innervate different target neuronal domains, and have a key role in regulating cortical neuronal activity. Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the cerebral cortex, and most cortical inhibitory synapses originate from non-pyramidal cells. Therefore, investigating the morphological and functional wiring properties of GABAergic non-pyramidal cells is critical to understanding the functional architecture of the cortical microcircuitry. This review focuses on current understanding of the different roles of inhibitory GABAergic non-pyramidal cell subtypes in cortical functions. © 2013 Elsevier Ltd.


Sanada T.M.,National Institute for Physiological science | DeAngelis G.C.,University of Rochester
Journal of Neuroscience | Year: 2014

Neural processing of 2D visual motion has been studied extensively, but relatively little is known about how visual cortical neurons represent visual motion trajectories that include a component toward or away from the observer (motion in depth). Psychophysical studies have demonstrated that humans perceive motion in depth based on both changes in binocular disparity over time (CD cue) and interocular velocity differences (IOVD cue). However, evidence for neurons that represent motion in depth has been limited, especially in primates, and it is unknown whether such neurons make use of CD or IOVD cues. We show that approximately one-half of neurons in macaque area MT are selective for the direction of motion in depth, and that this selectivity is driven primarily by IOVD cues, with a small contribution from the CD cue. Our results establish that area MT, a central hub of the primate visual motion processing system, contains a 3D representation of visual motion. © 2014 the authors.

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