Okazaki National Research Institute

Okazaki, Japan

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Mochizuki H.,National Institute for Physiological science | Tanaka S.,Nagoya Institute of Technology | Morita T.,National Institute for Physiological science | Wasaka T.,National Institute for Physiological science | And 2 more authors.
Journal of Neurophysiology | Year: 2014

Itch is an unpleasant sensation with the desire to scratch. Although it is well known that scratching itchy skin is pleasurable, the cerebral mechanisms underlying this phenomenon are poorly understood. We hypothesized that the reward system is associated with scratching-induced pleasantness. To investigate this hypothesis, a functional magnetic resonance imaging study was performed in 16 healthy subjects. Pleasantness was evoked by scratching the wrists where itch stimuli were applied, while scratching the dorsal forearms, far from itch stimuli, did not evoke pleasantness. Interestingly, pleasantness evoked by scratching activated not only the reward system (i.e., the striatum and midbrain) but also key regions of perception (i.e., the primary somatosensory cortex) and awareness of subjective feelings (i.e., the insular cortex), indicating that a broad network is involved in scratching-induced pleasantness. Moreover, although itch was suppressed by scratching, motorrelated regions such as the supplementary motor area, premotor cortex, and cerebellum showed significant activation when pleasantness was evoked. This activation could explain why scratchinginduced pleasantness potentially reinforces scratching behaviors. This study is the first to identify networks activated by scratching-induced pleasantness. The results of the present study provide important information on the cerebral mechanisms underlying why scratching itchy skin evokes pleasurable feelings that reinforce scratching behaviors. © 2014 the American Physiological Society.

Nakamura Y.,Doshisha University | Nakamura Y.,Okinawa Institute of Science and Technology | Nakamura Y.,Institute Pasteur Paris | Nakamura Y.,French National Center for Scientific Research | And 14 more authors.
Neuron | Year: 2015

Synaptic efficacy and precision are influenced by the coupling of voltage-gated Ca2+ channels (VGCCs) to vesicles. But because the topography of VGCCs and their proximity to vesicles is unknown, a quantitative understanding of the determinants of vesicular release at nanometer scale is lacking. To investigate this, we combined freeze-fracture replica immunogold labeling of Cav2.1 channels, local [Ca2+] imaging, and patch pipette perfusion of EGTA at the calyx of Held. Between postnatal day 7 and 21, VGCCs formed variable sized clusters and vesicular release became less sensitive to EGTA, whereas fixed Ca2+ buffer properties remained constant. Experimentally constrained reaction-diffusion simulations suggest that Ca2+ sensors for vesicular release are located at the perimeter of VGCC clusters (<30nm) and predict that VGCC number per cluster determines vesicular release probability without altering release time course. This "perimeter release model" provides a unifying framework accounting for developmental changes in both synaptic efficacy and time course. © 2015 The Authors.

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.

Um J.W.,Yonsei University | Pramanik G.,Shinshu University | Pramanik G.,Okazaki National Research Institute | Ko J.S.,Yonsei University | And 9 more authors.
Cell Reports | Year: 2014

Multiple synaptic adhesion molecules govern synapse formation. Here, we propose calsyntenin-3/alcadein-β as a synapse organizer that specifically induces presynaptic differentiation in heterologous synapse-formation assays. Calsyntenin-3 (CST-3) is highly expressed during various postnatal periods of mouse brain development. The simultaneous knockdown of all three CSTs, but not CST-3 alone, decreases inhibitory, but not excitatory, synapse densities in cultured hippocampal neurons. Moreover, the knockdown of CSTs specifically reduces inhibitory synaptic transmission invitro and invivo. Remarkably, the loss of CSTs induces a concomitant decrease in neuron soma size in a non-cell-autonomous manner. Furthermore, α-neurexins (α-Nrxs) are components of a CST-3 complex involved in CST-3-mediated presynaptic differentiation. However, CST-3 does not directly bind to Nrxs. Viewed together, these data suggest that the three CSTs redundantly regulate inhibitory synapse formation, inhibitory synapse function, and neuron development in concert with Nrxs. © 2014 The Authors.

Asano Y.,Kyushu University | Hiramoto T.,Kyushu University | Nishino R.,Tokai University | Aiba Y.,Tokai University | And 5 more authors.
American Journal of Physiology - Gastrointestinal and Liver Physiology | Year: 2012

There is increasing interest in the bidirectional communication between the mammalian host and prokaryotic cells. Catecholamines (CA), candidate molecules for such communication, are presumed to play an important role in the gut lumen; however, available evidence is limited because of the lack of actual data about luminal CA. This study evaluated luminal CA levels in the gastrointestinal tract and elucidated the involvement of gut microbiota in the generation of luminal CA by comparing the findings among specific pathogen-free mice (SPF-M), germ-free mice (GF-M), and gnotobiotic mice. Substantial levels of free dopamine and norepinephrine were identified in the gut lumen of SPF-M. The free CA levels in the gut lumen were lower in GF-M than in SPF-M. The majority of CA was a biologically active, free form in SPF-M, whereas it was a biologically inactive, conjugated form in GF-M. The association of GF-M with either Clostridium species or SPF fecal flora, both of which have abundant β-glucuronidase activity, resulted in the drastic elevation of free CA. The inoculation of E. coli strain into GF-M induced a substantial amount of free CA, but the inoculation of its mutant strain deficient in the β-glucuronidase gene did not. The intraluminal administration of DA increased colonic water absorption in an in vivo ligated loop model of SPF-M, thus suggesting that luminal DA plays a role as a proabsorptive modulator of water transport in the colon. These results indicate that gut microbiota play a critical role in the generation of free CA in the gut lumen. © 2012 the American Physiological Society.

Nagaoka T.,Okazaki National Research Institute | Kishi M.,Okazaki National Research Institute
Neuroscience Letters | Year: 2016

The excitatory postsynaptic region of the vertebrate hippocampus is usually compartmentalized into the postsynaptic density (PSD) and N-cadherin-rich domain, which is important for synaptic adhesion. However, the molecular mechanisms underlying the compartment formation are unknown. In the present report, we show that the planar cell polarity (PCP) protein Van Gogh-like 2 (Vangl2) plays a role in this regionalization. In cultured rat hippocampal neurons that were subjected to Vangl2 expression silencing, the formed clusters of PSD-95, one of the major scaffolding proteins in PSD, tended to overlap with those of N-cadherin. Further, in the dendrites of these neurons, the immunofluorescence of PSD-95 was to some extent diffused, without a significant change in the total signal. Because Vangl2 physically interacts with both PSD-95 and N-cadherin in vivo, these results suggest that a PCP-related direct molecular mechanism underlies the horizontal polarization of the postsynaptic regions. © 2015 Elsevier Ireland Ltd.

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 K.,Nagoya University | Shigemoto R.,Okazaki National Research Institute | Sokabe M.,Nagoya University
Cell and Tissue Research | Year: 2010

Subepithelial fibroblasts of the intestinal villi, which form a contractile cellular network beneath the epithelium, are in close contact with epithelial cells, nerve varicosities, capillaries, smooth muscles and immune cells, and secrete extracellular matrix molecules, growth factors and cytokines, etc. Cultured subepithelial fibroblasts of the rat duodenal villi display various receptors such as endothelins, ATP, substance-P and bradykinin, and release ATP in response to mechanical stimulation. In this study, the presence of functional NK1 receptors (NK1R) was pharmacologically confirmed in primary culture by Ca2+ measurement, and the effects of substance-P were measured in an acute preparation of epithelium-free duodenal villi from 2- to 3-week-old rats using a two-photon laser microscope. Substance-P elicited an increase in the intracellular Ca2+ concentration and contraction of the subepithelial fibroblasts in culture and the isolated villi. The localization of NK1R and substance-P in the villi was examined by light and electron microscopic immunohistochemistry. NK1R-like immunoreactivity was intensely localized on the plasma membrane of villous subepithelial fibroblasts in 10-day- to 4-week-old rats and mice and was decreased or absent in adulthood. The pericryptal fibroblasts of the small and large intestine were NK1R immuno-negative. These villous subepithelial fibroblasts form synapse-like structures with both substance-P-immunopositive and -immunonegative nerve varicosities. Here, we propose that the mutual interaction between villous subepithelial fibroblasts and afferent neurons via substance-P and ATP plays important roles in the maturation of the structure and function of the small intestine. © 2010 Springer-Verlag.

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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