Okazaki National Research Institute

Okazaki, Japan
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Miyahara M.,Okazaki National Research Institute | Miyahara M.,University of Otago | Harada T.,Nagoya University | Ruffman T.,University of Otago | And 2 more authors.
Social Cognitive and Affective Neuroscience | Year: 2013

The recognition of threatening faces is important for making social judgments. For example, threatening facial features of defendants could affect the decisions of jurors during a trial. Previous neuroimaging studies using faces of members of the general public have identified a pivotal role of the amygdala in perceiving threat. This functional magnetic resonance imaging study used face photographs of male prisoners who had been convicted of first-degree murder (MUR) as threatening facial stimuli. We compared the subjective ratings of MUR faces with those of control (CON) faces and examined how they were related to brain activation, particularly, the modulation of the functional connectivity between the amygdala and other brain regions. The MUR faces were perceived to be more threatening than the CON faces. The bilateral amygdala was shown to respond to both MUR and CON faces, but subtraction analysis revealed no significant difference between the two. Functional connectivity analysis indicated that the extent of connectivity between the left amygdala and the face-related regions (i.e. the superior temporal sulcus, inferior temporal gyrus and fusiform gyrus) was correlated with the subjective threat rating for the faces. We have demonstrated that the functional connectivity is modulated by vigilance for threatening facial features.©The Author (2011). Published by Oxford University Press.

Etherton M.,Stanford University | Etherton M.,University of Texas Southwestern Medical Center | Foldy C.,Stanford University | Sharma M.,Stanford University | And 8 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2011

Multiple independent mutations in neuroligin genes were identified in patients with familial autism, including the R451C substitution in neuroligin-3 (NL3). Previous studies showed that NL3 R451C knock-in mice exhibited modestly impaired social behaviors, enhanced water maze learning abilities, and increased synaptic inhibition in the somatosensory cortex, and they suggested that the behavioral changes in these mice may be caused by a general shift of synaptic transmission to inhibition. Here, we confirm that NL3 R451C mutant mice behaviorally exhibit social interaction deficits and electrophysiologically display increased synaptic inhibition in the somatosensory cortex. Unexpectedly, however, we find that the NL3 R451C mutation produced a strikingly different phenotype in the hippocampus. Specifically, in the hippocampal CA1 region, the NL3 R451C mutation caused an ∼1.5-fold increase in AMPA receptor-mediated excitatory synaptic transmission, dramatically altered the kinetics of NMDA receptor-mediated synaptic responses, induced an approximately twofold up-regulation of NMDA receptors containing NR2B subunits, and enhanced long-term potentiation almost twofold. NL3 KO mice did not exhibit any of these changes. Quantitative light microscopy and EM revealed that the NL3 R451C mutation increased dendritic branching and altered the structure of synapses in the stratum radiatum of the hippocampus. Thus, in NL3 R451C mutant mice, a single point mutation in a synaptic cell adhesion molecule causes context-dependent changes in synaptic transmission; these changes are consistent with the broad impact of this mutation on murine and human behaviors, suggesting that NL3 controls excitatory and inhibitory synapse properties in a region- and circuit-specific manner.

Koyama S.,Health Science University | Koyama S.,Okazaki National Research Institute | Nakagawa K.,Hiroshima University | Tanaka S.,Hamamatsu University School of Medicine
NeuroReport | Year: 2017

Transcranial magnetic stimulation (TMS) over the opercular somatosensory region (OP), which includes the secondary somatosensory cortex and the insular cortex, suppresses pain sensation. However, whether transcranial direct current stimulation (tDCS) over the OP has a similar effect on pain sensation remains unknown. We examined whether pain sensation would be suppressed by tDCS over the OP. Our experiment with a triple-blind, sham-controlled, crossover design involved 12 healthy participants. Participants were asked to rate their subjective pain intensity during and after three types of bihemispheric tDCS: right anodal/left cathodal OP tDCS, left anodal/right cathodal OP tDCS (2 mA, 12 min), and sham tDCS (15 s). Pain stimuli were alternately applied to the dorsum of each index finger using intraepidermal electrical stimulation. We observed no significant effect of tDCS over the OP on the perception of experimentally induced pain. Subjective pain intensity did not differ significantly between the three tDCS conditions. The present null results have crucial implications for the selection of optimal stimulation regions and parameters for clinical pain treatment. © 2017 Wolters Kluwer Health, Inc. All rights reserved.

Aramaki Y.,Chukyo University | Aramaki Y.,Nagoya Institute of Technology | Aramaki Y.,Japan National Institute of Information and Communications Technology | Haruno M.,Japan National Institute of Information and Communications Technology | And 2 more authors.
Journal of Neuroscience | Year: 2011

In periodic bimanual movements, anti-phase-coordinated patterns often change into in-phase patterns suddenly and involuntarily. Because behavior in the initial period of a sequence of cycles often does not show any obvious errors, it is difficult to predict subsequent movement errors in the later period of the cyclical sequence. Here, we evaluated performance in the later period of the cyclical sequence of bimanual periodic movements using human brain activity measured with functional magnetic resonance imaging as well as using initial movement features. Eighteen subjects performed a 30 s bimanual finger-tapping task. We calculated differences in initiationlocked transient brain activity between antiphase and in-phase tapping conditions. Correlation analysis revealed that the difference in the anterior putamen activity during antiphase compared within-phase tapping conditions was strongly correlated with future instability as measured by the mean absolute deviation of the left-hand intertap interval during antiphase movements relative to in-phase movements (r = 0.81). Among the initial movement features we measured, only the number of taps to establish the antiphase movement pattern exhibited a significant correlation. However, the correlation efficient of 0.60 was not high enough to predict the characteristics of subsequent movement. There was no significant correlation between putamen activity and initial movement features. It is likely that initiating unskilled difficult movements requires increased anterior putamen activity, and this activity increase may facilitate the initiation of movement via the basal ganglia-thalamocortical circuit. Our results suggest that initiation-locked transient activity of the anterior putamen can be used to predict future motor performance. © 2011 the authors.

Aoto J.,Stanford University | Foldy C.,Stanford University | Ilcus S.M.C.,Stanford University | Tabuchi K.,Stanford University | And 4 more authors.
Nature Neuroscience | Year: 2015

α- and β-neurexins are presynaptic cell-adhesion molecules whose general importance for synaptic transmission is well documented. The specific functions of neurexins, however, remain largely unknown because no conditional neurexin knockouts are available and targeting all α- and β-neurexins produced by a particular gene is challenging. Using newly generated constitutive and conditional knockout mice that target all neurexin-3α and neurexin-3β isoforms, we found that neurexin-3 was differentially required for distinct synaptic functions in different brain regions. Specifically, we found that, in cultured neurons and acute slices of the hippocampus, extracellular sequences of presynaptic neurexin-3 mediated trans-synaptic regulation of postsynaptic AMPA receptors. In cultured neurons and acute slices of the olfactory bulb, however, intracellular sequences of presynaptic neurexin-3 were selectively required for GABA release. Thus, our data indicate that neurexin-3 performs distinct essential pre- or postsynaptic functions in different brain regions by distinct mechanisms. © 2015 Nature America, Inc.

Izuma K.,Okazaki National Research Institute | Izuma K.,Graduate University for Advanced Studies | Saito D.N.,Okazaki National Research Institute | Sadato N.,Okazaki National Research Institute | And 3 more authors.
Journal of Cognitive Neuroscience | Year: 2010

Human behaviors are motivated not only by materialistic rewards but also by abstract social rewards, such as the approval of others. When choosing an action in social situations, to evaluate each action, the brain must convert different types of reward (such as money or social approval) into a common scale. Here using fMRI, we investigated the neural correlates of such valuation computations while individuals freely decided whether to donate to real charities or to take the money for themselves in the presence or absence of observers. Behavioral evidence showed that the mere presence of observers increased donation rates, and neuroimaging results revealed that activation in the ventral striatum before the same choice ("donate" or "not donate") was significantly modulated by the presence of observers. Particularly high striatal activations were observed when a high social reward was expected (donation in public) and when there was the potential for monetary gain without social cost (no donation in the absence of observers). These findings highlight the importance of this area in representing both social and monetary rewards as a "decision utility" and add to the understanding of how the brain makes a choice using a "common neural currency" in social situations. © 2009 Massachusetts Institute of Technology.

Sakamoto H.,Okayama University | Sakamoto H.,Kyoto Prefectural University of Medicine | Arii T.,Okazaki National Research Institute | Kawata M.,Kyoto Prefectural University of Medicine
Endocrinology | Year: 2010

The spinal nucleus of bulbocavernosus (SNB) is a sexually dimorphic motor nucleus located in the anterior horn of the fifth and sixth lumbar segments of the spinal cord that plays a significant role in male sexual function. We recently found that a sexually dimorphic expression of gastrin-releasing peptide (GRP) in the lumbar spinal cord regulates male copulatory reflexes. Although it is reported that these systems are both profoundly regulated by circulating androgen levels in male rats, no direct evidence has been reported regarding GRP synaptic inputs onto SNB motoneurons. The aim of the current study was to determine the axodendritic synaptic inputs of spinal GRP neurons to SNB motoneurons. Immunoelectron microscopy, combined with a retrograde tracing technique using high-voltage electron microscopy (HVEM), provided a three-dimensional visualization of synaptic contacts from the GRP system in the lumbar spinal cord onto SNB motoneurons. HVEM analysis clearly demonstrated that GRP-immunoreactive axon terminals directly contact dendrites that extend into the dorsal gray commissure from the SNB. These HVEM findings provide an ultrastructural basis for understanding how the spinal GRP system regulates male sexual behavior. Copyright © 2010 by The Endocrine Society.

Izuma K.,Tamagawa University | Izuma K.,California Institute of Technology | Matsumoto M.,Tamagawa University | Murayama K.,Ludwig Maximilians University of Munich | And 3 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

According to many modern economic theories, actions simply reflect an individual's preferences, whereas a psychological phenomenon called "cognitive dissonance" claims that actions can also create preference. Cognitive dissonance theory states that after making a difficult choice between two equally preferred items, the act of rejecting a favorite item induces an uncomfortable feeling (cognitive dissonance), which in turn motivates individuals to change their preferences to match their prior decision (i.e., reducing preference for rejected items). Recently, however, Chen and Risen [Chen K, Risen J (2010) J Pers Soc Psychol 99:573-594] pointed out a serious methodological problem, which casts a doubt on the very existence of this choice-induced preference change as studied over the past 50 y. Here, using a proper control condition and two measures of preferences (self-report and brain activity), we found that the mere act of making a choice can change self-report preference as well as its neural representation (i.e., striatum activity), thus providing strong evidence for choice-induced preference change. Furthermore, our data indicate that the anterior cingulate cortex and dorsolateral prefrontal cortex tracked the degree of cognitive dissonance on a trial-by-trial basis. Our findings provide important insights into the neural basis of how actions can alter an individual's preferences.

Etherton M.R.,Stanford University | Tabuchi K.,Stanford University | Tabuchi K.,Okazaki National Research Institute | Sharma M.,Stanford University | And 3 more authors.
EMBO Journal | Year: 2011

Neuroligins are evolutionarily conserved postsynaptic cell-adhesion molecules that function, at least in part, by forming trans-synaptic complexes with presynaptic neurexins. Different neuroligin isoforms perform diverse functions and exhibit distinct intracellular localizations, but contain similar cytoplasmic sequences whose role remains largely unknown. Here, we analysed the effect of a single amino-acid substitution (R704C) that targets a conserved arginine residue in the cytoplasmic sequence of all neuroligins, and that was associated with autism in neuroligin-4. We introduced the R704C mutation into mouse neuroligin-3 by homologous recombination, and examined its effect on synapses in vitro and in vivo. Electrophysiological and morphological studies revealed that the neuroligin-3 R704C mutation did not significantly alter synapse formation, but dramatically impaired synapse function. Specifically, the R704C mutation caused a major and selective decrease in AMPA receptor-mediated synaptic transmission in pyramidal neurons of the hippocampus, without similarly changing NMDA or GABA receptor-mediated synaptic transmission, and without detectably altering presynaptic neurotransmitter release. Our results suggest that the cytoplasmic tail of neuroligin-3 has a central role in synaptic transmission by modulating the recruitment of AMPA receptors to postsynaptic sites at excitatory synapses. © 2011 European Molecular Biology Organization | All Rights Reserved.

Furuya S.,Okazaki National Research Institute | Furuya K.,Nagoya University
International Review of Cell and Molecular Biology | Year: 2013

The ingestion of food and water induces chemical and mechanical signals that trigger peristaltic reflexes and also villous movement in the gut. In the intestinal villi, subepithelial fibroblasts under the epithelium form contractile cellular networks and closely contact to the varicosities of substance P and nonsubstance P afferent neurons. Subepithelial fibroblasts of the duodenal villi possess purinergic receptor P2Y1 and tachykinin receptor NK1. ATP and substance P induce increase in intracellular Ca2+ and cell contraction in subepithelial fibroblasts. They are highly mechanosensitive and release ATP by mechanical stimuli. Released ATP spreads to form an ATP "cloud" with nearly 1μM concentration and activates the surroundings via P2Y1 and afferent neurons via P2X receptors. These findings suggest that villous subepithelial fibroblasts and afferent neurons interact via ATP and substance P. This mutual interaction may play important roles in the signal transduction of mechano reflex pathways including a coordinate villous movement and also in the maturation of the structure and function of the intestinal villi. © 2013 Elsevier Inc.

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