Papers - Oka, Kotaro

Mechanical stimulus-evoked signal transduction between keratinocytes and sensory neurons via extracellular ATP

Shindo Y., Fujita K., Tanaka M., Fujio H., Hotta K., Oka K.

Biochemical and Biophysical Research Communications (Biochemical and Biophysical Research Communications)  582   131 - 136 2021.12

ISSN  0006291X

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The skin is exposed to various external stimuli. Keratinocytes, which are the main cell type in the epidermis, interact with peripheral sensory neurons and modulate neuronal activity. Recent studies have revealed that keratinocytes play crucial roles in nociception, and that ATP is one of the main mediators of signal transduction from keratinocytes to sensory neurons. However, no quantitative cellular level analyses of ATP-mediated information flow from keratinocytes to sensory dorsal root ganglion (DRG) neurons have been conducted. In this study, we performed simultaneous imaging of cell surface ATP and intracellular Ca2+ signals using both iATPSnFR, a genetically encoded ATP probe localized to the outside of the cell membrane, and the Ca2+ probe, Fura-red. Upon mechanical stimulation of the keratinocyte with a glass needle, an increase in Ca2+ and ATP release were observed around the stimulated area, and these phenomena were positively correlated. In cultured DRG neurons and keratinocytes neighboring the stimulated keratinocyte, increased intracellular Ca2+ concentration and levels of cell surface ATP on the side closer to the stimulated cell were detected. The ratio of Ca2+ response to input ATP signal was significantly larger in DRG neurons than in keratinocytes. We found that DRG neurons were more sensitive to ATP than keratinocytes, and therefore, only DRG neurons responded to ATP at 1 μM or lower concentrations when in co-culture with keratinocytes. Moreover, signals caused by moderate mechanical stimulation of keratinocytes were transmitted predominantly to DRG neurons. These findings would be important in the further determination of the detailed mechanism of nociception in the epidermis.

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Spatiotemporal dynamics of single cell stiffness in the early developing ascidian chordate embryo

Fujii Y., Koizumi W.C., Imai T., Yokobori M., Matsuo T., Oka K., Hotta K., Okajima T.

Communications Biology (Communications Biology)  4 ( 1 )  2021.12

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During the developmental processes of embryos, cells undergo massive deformation and division that are regulated by mechanical cues. However, little is known about how embryonic cells change their mechanical properties during different cleavage stages. Here, using atomic force microscopy, we investigated the stiffness of cells in ascidian embryos from the fertilised egg to the stage before gastrulation. In both animal and vegetal hemispheres, we observed a Rho kinase (ROCK)-independent cell stiffening that the cell stiffness exhibited a remarkable increase at the timing of cell division where cortical actin filaments were organized. Furthermore, in the vegetal hemisphere, we observed another mechanical behaviour, i.e., a ROCK-associated cell stiffening, which was retained even after cell division or occurred without division and propagated sequentially toward adjacent cells, displaying a characteristic cell-to-cell mechanical variation. The results indicate that the mechanical properties of embryonic cells are regulated at the single cell level in different germ layers.

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Peripheral-neuron-like properties of differentiated human dental pulp stem cells (hDPSCs)

Arimura Y., Shindo Y., Yamanaka R., Mochizuki M., Hotta K., Nakahara T., Ito E., Yoshioka T., Oka K.

PLoS ONE (PLoS ONE)  16 ( 5 May )  2021.05

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Elucidating the mechanisms underlying human pain sensation requires the establishment of an in vitro model of pain reception comprising human cells expressing pain-sensing receptors and function properly as neurons. Human dental pulp stem cells (hDPSCs) are mesenchymal stem cells and a promising candidate for producing human neuronal cells, however, the functional properties of differentiated hDPSCs have not yet been fully characterized. In this study, we demonstrated neuronal differentiation of hDPSCs via both their expression of neuronal marker proteins and their neuronal function examined using Ca2+ imaging. Moreover, to confirm the ability of nociception, Ca2+ responses in differentiated hDPSCs were compared to those of rat dorsal root ganglion (DRG) neurons. Those cells showed similar responses to glutamate, ATP and agonists of transient receptor potential (TRP) channels. Since TRP channels are implicated in nociception, differentiated hDPSCs provide a useful in vitro model of human peripheral neuron response to stimuli interpreted as pain.

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Small molecule-based alkaline-earth metal ion fluorescent probes for imaging intracellular and intercellular multiple signals

Hiruta Y., Shindo Y., Oka K., Citterio D.

Chemistry Letters (Chemistry Letters)  50 ( 5 ) 870 - 887 2021.05

ISSN  03667022

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This highlight review overviews recent progress in fluorescence imaging technology for the alkaline-earth metal ions calcium, and magnesium, by small molecule-based fluorescent probes. Fluorescent probes for Ca2+ using 1,2-bis-(o-aminophenoxy)- ethane-N,N,N′,N′-tetraacetic acid (BAPTA) as a recognition unit are introduced. Focus is set on the fluorescence characteristics and intracellular dynamics of Ca2+ fluorescent probes depending on the differences in fluorophore units. In addition, this review comprehensively covers Mg2+ fluorescent probes from Mg2+ selective ligands and fluorophore units to their application. In particular, the influence of the molecular structure of the fluorescent probes on organelle localization and fluorescence wavelength for imaging intracellular signals in organelles and intercellular multiple signal interactions are summarized, providing a strategy for probe design for chemists, and for selecting the appropriate imaging technique for biologists.

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High responsiveness of auditory neurons to specific combination of acoustic features in female songbirds

Inda M., Hotta K., Oka K.

European Journal of Neuroscience (European Journal of Neuroscience)  53 ( 5 ) 1412 - 1427 2021.03

ISSN  0953816X

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Zebra finch (Taeniopygia guttata) is a songbird species in which males sing their unique songs to attract females who then select their preferred male. Acoustic features in the songs of individual males are important features for female auditory perception. While the male of this species is a classic model of vocal production, it has been little known about auditory processing in female. In the higher auditory brain regions, the caudomedial mesopallium (CMM) and nidopallium (NCM) contribute to female's sound recognition, we, therefore, extracted acoustic features that induce neural activities with high detection power on both regions in female finches. A multiple linear regression analysis revealed that neurons were sensitive to mean frequency and Wiener entropy. In addition, we performed an experiment with modified artificial songs and harmonic songs to directly investigate neural responsiveness for deriving further evidence for the contribution of these two acoustic features. Finally, we illustrated a specific ratio combining these two acoustic features that showed highest sensitivity to neural responsiveness, and we found that properties of sensitivity are different between CMM and NCM. Our results indicate that the mixture of the two acoustic features with the specific ratio is important in the higher auditory regions of female songbirds, and these two regions have differences in encoding for sensitivity to these acoustic features.

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Two-Round Ca 2+ transient in papillae by mechanical stimulation induces metamorphosis in the ascidian Ciona intestinalis type A

Wakai M.K., Nakamura M.J., Sawai S., Hotta K., Oka K.

Proceedings of the Royal Society B: Biological Sciences (Proceedings of the Royal Society B: Biological Sciences)  288 ( 1945 )  2021.02

ISSN  09628452

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Marine invertebrate larvae are known to begin metamorphosis in response to environmentally derived cues. However, little is known about the relationships between the perception of such cues and internal signalling for metamorphosis. To elucidate the mechanism underlying the initiation of metamorphosis in the ascidian, Ciona intestinalis type A (Ciona robusta), we artificially induced ascidian metamorphosis and investigated Ca 2+ dynamics from pre- to post-metamorphosis. Ca 2+ transients were observed and consisted of two temporally distinct phases with different durations before tail regression which is the early event of metamorphosis. In the first phase, Phase I, the Ca 2+ transient in the papillae (adhesive organ of the anterior trunk) was coupled with the Ca 2+ transient in dorsally localized cells and endoderm cells just after mechanical stimulation. The Ca 2+ transients in Phase I were also observed when applying only short stimulation. In the second phase, Phase II, the Ca 2+ transient in papillae was observed again and lasted for approximately 5-11 min just after the Ca 2+ transient in Phase I continued for a few minutes. The impaired papillae by Foxg-knockdown failed to induce the second Ca 2+ transient in Phase II and tail regression. In Phase II, a wave-like Ca 2+ propagation was also observed across the entire epidermis. Our results indicate that the papillae sense a mechanical cue and two-round Ca 2+ transients in papillae transmits the internal metamorphic signals to different tissues, which subsequently induces tail regression. Our study will help elucidate the internal mechanism of metamorphosis in marine invertebrate larvae in response to environmental cues.

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Activation of the orbitofrontal cortex by both meditation and exercise: A near-infrared spectroscopy study

Miyashiro S., Yamada Y., Muta T., Ishikawa H., Abe T., Hori M., Oka K., Koshikawa F., Ito E.

PLoS ONE (PLoS ONE)  16 ( 2 February )  2021.02

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In some types of meditation, such as mindfulness and Zen, breathing is the focus of attention, whereas during an excessive, short-period of anaerobic exercise, the muscles become the focus of attention. Thus, during both efforts, one's attention is focused on a certain feature of the body. Both meditation and exercise generally provide mental refreshment to humans. We hypothesized that the same brain regions are activated by both efforts in humans. To examine this hypothesis, we engaged participants in 3 tasks: meditation, exercise, and a control task. After each task, the participants underwent a 2-back test to concentrate their thoughts, while changes in their blood hemoglobin levels were simultaneously monitored using near-infrared spectroscopy (NIRS). Seventeen participants (20-24 years of age; 11 men, 6 women) were enrolled. We applied a fast-Fourier transform (FFT) analysis to the NIRS wave data and calculated the correlation coefficients of the FFT data between (1) meditation and control, (2) exercise and control, and (3) meditation and exercise, at the orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC), brain areas that are generally involved in mental refreshment. A significant difference in the correlation coefficients between the OFC and DLPFC was detected in the meditation and exercise analysis, and signal source analysis confirmed that the NIRS waves spread from the right and left OFC edges (i.e., right and left temples) toward the center. Our results suggest that both meditation and exercise activate the OFC, which is involved in emotional reactions and motivation behavior, resulting in mental refreshment.

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Phylogenetic comparison of egg transparency in ascidians by hyperspectral imaging

Shito T.T., Hasegawa N., Oka K., Hotta K.

Scientific Reports (Scientific Reports)  10 ( 1 )  2020.12

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The transparency of animals is an important biological feature. Ascidian eggs have various degrees of transparency, but this characteristic has not yet been measured quantitatively and comprehensively. In this study, we established a method for evaluating the transparency of eggs to first characterize the transparency of ascidian eggs across different species and to infer a phylogenetic relationship among multiple taxa in the class Ascidiacea. We measured the transmittance of 199 eggs from 21 individuals using a hyperspectral camera. The spectrum of the visual range of wavelengths (400–760 nm) varied among individuals and we calculated each average transmittance of the visual range as bio-transparency. When combined with phylogenetic analysis based on the nuclear 18S rRNA and the mitochondrial cytochrome c oxidase subunit I gene sequences, the bio-transparencies of 13 species were derived from four different families: Ascidiidae, Cionidae, Pyuridae, and Styelidae. The bio-transparency varied 10–90% and likely evolved independently in each family. Ascidiella aspersa showed extremely high (88.0 ± 1.6%) bio-transparency in eggs that was maintained in the “invisible” larva. In addition, it was indicated that species of the Ascidiidae family may have a phylogenetic constraint of egg transparency.

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Rapid differentiation of human dental pulp stem cells to neuron-like cells by high K⁺ stimulation.

Kogo Y, Seto C, Totani Y, Mochizuki M, Nakahara T, Oka K, Yoshioka T, Ito E.

Biophysics and Physicobiology.  2020.09

Research paper (scientific journal), Joint Work, Accepted

Inhibition of Mg²⁺ Extrusion Attenuates Glutamate Excitotoxicity in Cultured Rat Hippocampal Neurons.

Shindo Y, Yamanaka R, Hotta K, Oka K.

Nutrients (Nutrients)  12 ( 9 ) 2768/1 - 2768/14 2020.09

Research paper (scientific journal), Joint Work, Accepted

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Magnesium plays important roles in the nervous system. An increase in the Mg2+ concentration in cerebrospinal fluid enhances neural functions, while Mg2+ deficiency is implicated in neuronal diseases in the central nervous system. We have previously demonstrated that high concentrations of glutamate induce excitotoxicity and elicit a transient increase in the intracellular concentration of Mg2+ due to the release of Mg2+ from mitochondria, followed by a decrease to below steady-state levels. Since Mg2+ deficiency is involved in neuronal diseases, this decrease presumably affects neuronal survival under excitotoxic conditions. However, the mechanism of the Mg2+ decrease and its effect on the excitotoxicity process have not been elucidated. In this study, we demonstrated that inhibitors of Mg2+ extrusion, quinidine and amiloride, attenuated glutamate excitotoxicity in cultured rat hippocampal neurons. A toxic concentration of glutamate induced both Mg2+ release from mitochondria and Mg2+ extrusion from cytosol, and both quinidine and amiloride suppressed only the extrusion. This resulted in the maintenance of a higher Mg2+ concentration in the cytosol than under steady-state conditions during the ten-minute exposure to glutamate. These inhibitors also attenuated the glutamate-induced depression of cellular energy metabolism. Our data indicate the importance of Mg2+ regulation in neuronal survival under excitotoxicity.

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Cellular thermogenesis compensates environmental temperature fluctuations for maintaining intracellular temperature.

Yamanaka R, Shindo Y, Hotta K, Hiroi N, Oka K.

Biochem Biophys Res Commun. (Biochemical and Biophysical Research Communications)  533 ( 1 ) 70 - 76 2020.08

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0006291X

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Temperature governs states and dynamics of all biological molecules, and several cellular processes are often heat sources and/or sinks. Technical achievement of intracellular thermometry enables us to measure intracellular temperature, and it can offer novel perspectives in biology and medicine. However, little is known that changes of intracellular temperature throughout the cell-cycle and the manner of which cells regulates their thermogenesis in response to fluctuation of the environmental temperature. Here, cell-cycle-dependent changes of intracellular temperature were reconstructed from the snapshots of cell population at single-cell resolution using ergodic analysis for asynchronously cultured HeLa cells expressing a genetically encoded thermometry. Intracellular temperature is highest at G1 phase, and it gradually decreases along cell-cycle progression and increases abruptly during mitosis. Cells easily heated up are harder to cool down and vice versa, especially at G1/S phases. Together, intracellular thermogenesis depends on cell-cycle phases and it maintains intracellular temperature through compensating environmental temperature fluctuations.

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Near-infrared pH responsive heptamethine cyanine platforms: Modulating the proton acceptor.

Kurutosab A, Shindo Y, Hiruta Y, Oka K, Citterio D.

Dyes and Pigments (Dyes and Pigments)  181 2020.05

Research paper (scientific journal), Joint Work, Accepted,  ISSN  01437208

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In this report, we wish to present the rational design, synthesis, and study of optical characteristics of near-infrared (NIR) molecular probes emitting over 800 nm. The title pH sensing platforms consist of a piperazine moiety serving as a hydronium ion receptor, coupled with a rigidified symmetric heptamethine backbone. The spectrally fine-tuned response of the fluorophores was studied in both organic solvents and aqueous buffer solutions, employing combined UV–Vis and steady state fluorimetric techniques. In parallel, computational approach and optical spectroscopy were employed aiming to ascribe the origin of spectral behavior of the amino-substituted heptamethines. Herein, we also investigated the halochromic effect of the differently substituted piperazines on the spectral properties of the NIR cyanine dyes. Under acidic conditions, the protonation of the piperazine moiety promoted a gradual bathochromic shift in the absorption spectra. The Δλ between the neutral and the protonated forms are indirectly related to the modifications applied to the proton acceptor. The calculated pKa values (5.13–7.06) were found to be dependent on the dye chemical structure. A good linear correlation was established between the pKa of the newly synthesized dyes and that of the reported piperazine moieties. This aspect allows the future expansion of the current facile strategy since sensing chromophores with predicted pH response could readily be designed based on pKa databases for substituted piperazine derivatives. A detailed literature study along with NMR and computational methods were found to be in agreement with our assumption, that both nitrogen atoms of the 1,4-disubstituted amine are involved in the sensing process. The covered pKa range allows us to recommend the title fluorophores as promising potential candidates for qualitative analysis of biological samples. A cytotoxicity study by the MTT assay showed that the NIR dyes are safe and applicable for bioanalytical purposes at dye concentrations up to 10 μM. Fluorescence imaging and cellular applications, including staining and visualization of HeLa cervical cancer cells was successfully demonstrated.

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Different strategies for tissue scaling in dwarf tailbud embryos revealed by single-cell analysis.

Matsumura KD, Nakamura MJ, Koizumi WC, Hotta K, Oka K.

Developmental biology. (Developmental Biology)  406 ( 2 ) 215 - 223 2020.04

Research paper (scientific journal), Joint Work, Accepted,  ISSN  00121606

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The tailbud stage is part of the organogenesis period—an evolutionarily conserved developmental period among chordates that is essential for determining the characteristics of the chordate body plan. When the volume of the egg is artificially decreased by cutting, ascidians produce a normal-looking but miniature (dwarf) tailbud embryo. Although cell lineages during ascidian embryogenesis are invariant, the number of cell divisions in the dwarf embryo is altered by a different mechanism in each tissue (Yamada and Nishida, 1999). Here, to elucidate the size-regulation strategies of the Ciona robusta dwarf tailbud embryo, we compared anatomical structure, developmental speed, and cell number/volume in each tissue between dwarf and wild type (WT) embryos. To do this, we constructed a 3D virtual mid-tailbud embryo (Nakamura et al., 2012). We could make a Ciona dwarf tailbud embryo from eggs with a diameter over 108 ​μm (correspond to ​> ​40% of the wild type egg volume). The timings of cleavage (~St. 12) and subsequent morphogenesis were nearly the same but blastomeres of animal hemisphere slightly delayed the timing of mitosis in the early cleavage period. Intriguingly, the tissue-to-tissue volume ratios of dwarf tailbud embryos were similar to those of wild type embryos suggesting that the ratio of tissue volumes is essential for maintaining the proper shape of the tailbud embryo. The number of cells in the epidermis, nervous system, and mesenchyme was significantly reduced in the dwarf embryos whereas the cell volume distribution of these tissues was similar in the dwarf and wild type. In contrast, the number of cells in the notochord, muscle, heart, and endoderm were maintained in the dwarf embryos; cell volumes were significantly reduced. Neither parameter changed in germline precursors. These results indicate that each tissue uses different scaling strategies to coordinate cell number and cell volume in accordance with the embryo size.

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Optical Dissection of Synaptic Plasticity for Early Adaptation in Caenorhabditis elegans

Ashida K., Shidara H., Hotta K., Oka K.

Neuroscience (Neuroscience)  428   112 - 121 2020.01

ISSN  03064522

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To understand neuronal information processing, it is essential to investigate the input–output relationship and its modulation via detailed dissections of synaptic transmission between pre- and postsynaptic neurons. In Caenorhabditis elegans, pre-exposure to an odorant for five minutes reduces chemotaxis (early adaptation). AWC sensory neurons and AIY interneurons are crucial for this adaptation; AWC neurons sense volatile odors, and AIY interneurons receive glutamatergic inputs from AWC neurons. However, modulations via early adaptation of the input–output relationship between AWC and AIY are not well characterized. Here we use a variety of fluorescent imaging techniques to show that reduced synaptic-vesicle release without Ca2+ modulation in AWC neurons suppresses the Ca2+ response in AIY neurons via early adaptation. First, early adaptation modulates the Ca2+ response in AIY but not AWC neurons. Adaptation in the Ca2+ signal measured in AIY neurons is caused by adaptation in glutamate release from AWC neurons. Further, we found that a G protein γ-subunit, GPC-1, is related to modulation of glutamate input to AIY. Our results dissect the modulation of the pre- and postsynaptic relationship in vivo based on optical methods, and demonstrate the importance of neurotransmitter-release modulation in presynaptic neurons without Ca2+ modulation.

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Near-Infrared Fluorescent Probes for Imaging of Intracellular Mg²⁺ and Application to Multi-Color Imaging of Mg²⁺, ATP, and Mitochondrial Membrane Potential.

Murata O, Shindo Y, Ikeda Y, Iwasawa N, Citterio D, Oka K, Hiruta Y.

Analytical chemistry. (Analytical Chemistry)  92 ( 1 ) 966 - 974 2020.01

Research paper (scientific journal), Joint Work, Accepted,  ISSN  00032700

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The magnesium ion (Mg2+) is an essential cation to maintain proper cellular activities. To visualize the dynamics and functions of Mg2+, there is a great need for the development of Mg2+-selective fluorescent probes. However, conventional Mg2+ fluorescent probes are falling behind in low selectivity and poor fluorescence color variation. In this report, to make available a distinct color window for multi-color imaging, we designed and synthesized highly Mg2+-selective and near-infrared (NIR) fluorescent probes, the KMG-500 series consisting of a charged β-diketone as a selective binding site for Mg2+ and a Si-rhodamine residue as the NIR fluorophore, which showed photoinduced electron transfer (PeT)-type OFF-ON response to the concentration of Mg2+. Two types of KMG-500 series probes, tetramethyl substituted Si-rhodamine KMG-501 and tetraethyl substituted Si-rhodamine KMG-502, were synthesized for the evaluation of cell permeability. For intracellular application, the membrane-permeable acetoxymethyl derivative KMG-501 (KMG-501AM) was synthesized and allowed to stably stain cultured rat hippocampal neurons during imaging of intracellular Mg2+. On the other hand, KMG-502 was cell membrane permeable without AM modification, preventing the probe from staying inside cells during imaging. KMG-501 distributed mainly in the cytoplasm and partially localized in lysosomes and mitochondria in cultured rat hippocampal neurons. Mg2+ increase in response to the FCCP uncoupler inducing depolarization of the mitochondrial inner membrane potential was detected in the KMG-501 stained neurons. For the first time, KMG-501 succeeded in imaging intracellular Mg2+ dynamics with NIR fluorescence. Moreover, it allows one to simultaneously visualize changes in Mg2+ and ATP concentration and also mitochondrial inner membrane potential and their interactions. This probe is expected to be a strong tool for multi-color imaging of intracellular Mg2+

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Serotonin modulates behavior-related neural activity of RID interneuron in Caenorhabditis elegans.

Mori H, Ashida K, Shidara H, Nikai T, Hotta K, Oka K.

PLoS ONE (PLoS ONE)  14 ( 12 )  2019.12

Research paper (scientific journal), Joint Work, Accepted

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Animals change their behaviors in response to external stimuli, and numerous neurotransmitters are involved in these behavioral changes. In Caenorhabditis elegans, serotonin (5- HT) affects various behaviors such as inhibition of locomotion, stimulation of egg laying, and pharyngeal pumping. Previous research has shown that the neural activity of the RID interneuron increases when the worm moves forward, and the RID is necessary for sustaining forward locomotion. However, the relationship between 5-HT and neural activity of RID, and how it modulates the behavior of the worm has not been investigated. In this article, we reveal the relationship among 5-HT, RID activity, and the behavior of worms using a custom- made tracking and imaging system. We simultaneously measured the neural activity of the RID and behavior in worms with three conditions: mock animals, animals pre-exposed to 5-HT, and 5-HT receptor mod-1 mutants. As shown in previous research, the neural activity of the RID increased during the transition from backward to forward, whereas it decreased during the transition from forward to backward in mock animals. These changes in neural activity were not observed in animals pre-exposed to 5-HT and mod-1 mutants. Moreover, RID activity was correlated with the velocity of the worm in mock animals. However, this correlation was not observed in animals pre-exposed to 5-HT and mod-1 mutants. Our results demonstrate that 5-HT modulates the activity of the RID interneuron, and we infer that the RID plays a role in modulating forward locomotion by changing its activity through 5-HT.

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Neural properties of fundamental function encoding of sound selectivity in the female avian auditory cortex. The European journal of neuroscience.

Inda M, Hotta K, Oka K.

The European journal of neuroscience. (European Journal of Neuroscience)  51 ( 8 ) 1770 - 1783 2019.11

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0953816X

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Zebra finches (Taeniopygia guttata) use their voices for communication. Song structures in the songs of individual males are important for sound recognition in females. The caudomedial mesopallium (CMM) and nidopallium (NCM) are known to be essential higher auditory regions for sound recognition. These two regions have also been discussed with respect to their fundamental functions and song selectivity. To clarify their functions and selectivity, we investigated latencies and spiking patterns and also developed a novel correlation analysis to evaluate the relationship between neural activity and the characteristics of acoustic factors. We found that the latencies and spiking patterns in response to song stimuli differed between the CMM and NCM. In addition, our correlation analysis revealed that amplitude and frequency structures were important temporal acoustic factors for both regions. Although the CMM and NCM have different fundamental functions, they share similar encoding systems for acoustic factors.

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Food deprivation changes chemotaxis behavior in Caenorhabditis elegans.

Shimizu K, Ashida K, Hotta K, Oka K.

Biophys Physicobiol 2019 16   167 - 172 2019.11

Research paper (scientific journal), Joint Work, Accepted

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The Input-Output Relationship of AIY Interneurons in Caenorhabditis elegans in Noisy Environment.

Ashida K, Hotta K, Oka K

iScience (iScience)  19   191 - 203 2019.09

Research paper (scientific journal), Joint Work, Accepted

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Determining how neurotransmitter input causes various neuronal activities is crucial to understanding neuronal information processing. In Caenorhabditis elegans, AIY interneurons receive several sources of sensory information as glutamate inputs and regulate behavior by integrating these inputs. However, the relationship between glutamate input and the Ca2+ response in AIY under environmental noise, in other words, without explicit stimulation, remains unknown. Here, we show that glutamate-input fluctuations evoke a sporadic Ca2+ response in AIY without stimulation. To ensure that Ca2+ response can be considered AIY output, we show that the membrane-potential depolarization precedes Ca2+ responses in AIY. We used an odor as model stimulation to modulate the sensory inputs. Simultaneous imaging of glutamate input and Ca2+ response, together with glutamate transmission mutants, showed that glutamate-input fluctuations evoke sporadic Ca2+ responses. We identified the input-output relationships under environmental noise in vivo, and our results address the relationship between sensory-input fluctuations and behavioral variability. Neuroscience; Systems Neuroscience; Sensory Neuroscience

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Multiple tracking and machine learning reveal dopamine modulation for area-restricted foraging behaviors via velocity change in Caenorhabditis elegans.

Ashida K, Kato T, Hotta K, Oka K

Neuroscience letters. (Neuroscience Letters)  706   68 - 74 2019.07

Research paper (scientific journal), Joint Work, Accepted,  ISSN  03043940

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Food exploration is an essential survival behavior in organisms. To find food efficiently, many organisms use a foraging strategy called area-restricted search (ARS) wherein individuals first turn more frequently, restricting their search to one area, then turn less frequently, moving along a straight path to widen the search area. Previous research suggests that the nematode Caenorhabditis elegans shows ARS behavior by changing turn frequency, and that dopamine is a crucial determinant. However, the effects of dopamine on multiple behavioral parameters have remained unknown. Here, we evaluated turn (pirouette) frequency, moving velocity, and specific area occupancy (cell occupancy) over time by using a multiple-worms tracking system. In the control (mock) experiments, all parameters changed over time, but no changes were observed in experiments with dopamine pre-exposed and dopamine-deficient animals. In inverse reinforcement learning analysis, the value function for specific velocity was found to modulate over time in mock animals only. These results demonstrate that dopamine regulates ARS via changes not only to pirouette frequency change but also to velocity.

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Magnesium Is a Key Player in Neuronal Maturation and Neuropathology.

Yamanaka R, Shindo Y, Oka K

International journal of molecular sciences. (International Journal of Molecular Sciences)  20 ( 14(3439) )  2019.07

Research paper (scientific journal), Joint Work, Accepted,  ISSN  16616596

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Magnesium (Mg) is the second most abundant cation in mammalian cells, and it is essential for numerous cellular processes including enzymatic reactions, ion channel functions, metabolic cycles, cellular signaling, and DNA/RNA stabilities. Because of the versatile and universal nature of Mg2+, the homeostasis of intracellular Mg2+ is physiologically linked to growth, proliferation, differentiation, energy metabolism, and death of cells. On the cellular and tissue levels, maintaining Mg2+ within optimal levels according to the biological context, such as cell types, developmental stages, extracellular environments, and pathophysiological conditions, is crucial for development, normal functions, and diseases. Hence, Mg2+ is pathologically involved in cancers, diabetes, and neurodegenerative diseases, such as Parkinson’s disease, Alzheimer’s disease, and demyelination. In the research field regarding the roles and mechanisms of Mg2+ regulation, numerous controversies caused by its versatility and complexity still exist. As Mg2+, at least, plays critical roles in neuronal development, healthy normal functions, and diseases, appropriate Mg2+ supplementation exhibits neurotrophic effects in a majority of cases. Hence, the control of Mg2+ homeostasis can be a candidate for therapeutic targets in neuronal diseases. In this review, recent results regarding the roles of intracellular Mg2+ and its regulatory system in determining the cell phenotype, fate, and diseases in the nervous system are summarized, and an overview of the comprehensive roles of Mg2+ is provided.

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Stochastic thermodynamic limit on E. coli adaptation by information geometric approach.

Ashida K, Oka K

Biochemical and biophysical research communications. (Biochemical and Biophysical Research Communications)  15 ( 508(3) ) 690 - 694 2018.12

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0006291X

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Biological systems process information under noisy environment. Sensory adaptation model of E. coli is suitable for investigation because of its simplicity. To understand the adaptation processing quantitatively, stochastic thermodynamic approach has been attempted. Information processing can be assumed as state transition of a system that consists of signal transduction molecules using thermodynamic approach, and efficiency can be measured as thermodynamic cost. Recently, using information geometry and stochastic thermodynamics, a relationship between speed of the transition and the thermodynamic cost has been investigated for a chemical reaction model. Here, we introduce this approach to sensory adaptation model of E. coli, and examined a relationship between adaptation speed and the thermodynamic cost, and efficiency of the adaptation speed. For increasing external noise level in stimulation, the efficiency decreased, but the efficiency was highly robust to external stimulation strength. Moreover, we demonstrated that there is the best noise to achieve the adaptation in the aspect of thermodynamic efficiency. Our quantification method provides a framework to understand the adaptation speed and the thermodynamic cost for various biological systems.

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GABA-Induced Intracellular Mg²⁺ Mobilization Integrates and Coordinates Cellular Information Processing for the Maturation of Neural Networks.

Yamanaka R, Shindo Y, Hotta K, Suzuki K, Oka K

Current biology (Current Biology)  28 ( 24 ) 3984 - 3991 2018.11

Research paper (scientific journal), Joint Work, Accepted,  ISSN  09609822

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Yamanaka et al. demonstrate that GABA triggers mitochondrial Mg 2+ release in neurons at specifically developmental early stages, and the physiological Mg 2+ redistribution into cytoplasm regulates ERK, CREB, and mTOR activities with target-dependent manners, thereby facilitating neuronal maturation. Mg 2+ is a novel signal transducer.

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14-3-3εa directs the pulsatile transport of basal factors toward the apical domain for lumen growth in tubulogenesis.

Mizotani Y, Suzuki M, Hotta K, Watanabe H, Shiba K, Inaba K, Tashiro E, Oka K, Imoto M

Proceedings of the National Academy of Sciences of the United States of America (Proceedings of the National Academy of Sciences of the United States of America)  115 ( 38 ) E8873 - E8881 2018.09

Research paper (scientific journal), Joint Work, Accepted,  ISSN  00278424

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The Ciona notochord has emerged as a simple and tractable in vivo model for tubulogenesis. Here, using a chemical genetics approach, we identified UTKO1 as a selective small molecule inhibitor of notochord tubulogenesis. We identified 14-3-3ϵa protein as a direct binding partner of UTKO1 and showed that 14-3-3ϵa knockdown leads to failure of notochord tubulogenesis. We found that UTKO1 prevents 14-3-3ϵa from interacting with ezrin/radixin/moesin (ERM), which is required for notochord tubulogenesis, suggesting that interactions between 14-3-3ϵa and ERM play a key role in regulating the early steps of tubulogenesis. Using live imaging, we found that, as lumens begin to open between neighboring cells, 14-3-3ϵa and ERM are highly colocalized at the basal cortex where they undergo cycles of accumulation and disappearance. Interestingly, the disappearance of 14-3-3ϵa and ERM during each cycle is tightly correlated with a transient flow of 14-3-3ϵa, ERM, myosin II, and other cytoplasmic elements from the basal surface toward the lumen-facing apical domain, which is often accompanied by visible changes in lumen architecture. Both pulsatile flow and lumen formation are abolished in larvae treated with UTKO1, in larvae depleted of either 14-3-3ϵa or ERM, or in larvae expressing a truncated form of 14-3-3ϵa that lacks the ability to interact with ERM. These results suggest that 14-3-3ϵa and ERM interact at the basal cortex to direct pulsatile basal accumulation and basal-apical transport of factors that are essential for lumen formation. We propose that similar mechanisms may underlie or may contribute to lumen formation in tubulogenesis in other systems.

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Effect of interactions among individuals on the chemotaxis behaviours of Caenorhabditis elegans

Yoshimizu T, Shidara H, Ashida K, Hotta K, Oka K

The Journal of experimental biology 2018 (Journal of Experimental Biology)  221 ( 11 )  2018.06

Research paper (scientific journal), Joint Work, Accepted,  ISSN  00220949

　View Summary

In many species, individual social animals interact with others in their group and change their collective behaviours. For the solitary nematode Caenorhabditis elegans strain N2, previous research suggests that individuals can change the behaviour of other worms via pheromones and mechanosensory interactions. In particular, pheromones affect foraging behaviour, so that the chemotactic behaviours of individuals in a group (population) can be modulated by interactions with other individuals in the population. To investigate this, we directly compared the chemotactic behaviours of isolated (single) worms with those of individual animals within a population. We found that worms approached an odour source in a distinct manner depending on whether they were alone or in a population. Analysis of behaviours of the N2 worm and a pheromone production-defective mutant revealed that the 'pirouette' strategy was modulated by interaction of the worms via pheromones. Thus, pheromones play an important role in the characteristic collective behaviours seen in the population condition.

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Transitional correlation between inner-membrane potential and ATP levels of neuronal mitochondria.

Suzuki R, Hotta K, Oka K.

Scientific Reports. (Scientific Reports)  8 ( 1 ) 2993 2018.02

Research paper (scientific journal), Joint Work, Accepted

　View Summary

The importance of highly active mitochondria and their contribution to neuronal function has been of recent interest. In most cases, however, mitochondrial activity is estimated using measurements of mitochondrial inner membrane potential (IMPmito), and little is known about the dynamics of native mitochondrial ATP (ATPmito). This study conducted simultaneous imaging of IMPmito and ATPmito in neurons to explore their behaviour and their correlation during physiological mitochondrial/neuronal activity. We found that mitochondrial size, transport velocity and transport direction are not dependent on ATPmito or IMPmito. However, changes in ATPmito and IMPmito during mitochondrial fission/fusion were found; IMPmito depolarized via mitochondrial fission and hyperpolarized via fusion, and ATPmito levels increased after fusion. Because the density of mitochondria is higher in growth cones (GCs) than in axonal processes, integrated ATPmito signals (density × ATPmito) were higher in GCs. This integrated signal in GCs correlated with axonal elongation. However, while the averaged IMPmito was relatively hyperpolarized in GCs, there was no correlation between IMPmito in GCs and axonal elongation. A detailed time-course analysis performed to clarify the reason for these discrepancies showed that IMPmito and ATPmito levels did not always correlate accurately; rather, there were several correlation patterns that changed over time.

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A Transient Rise in Free Mg²⁺ Ions Released from ATP-Mg Hydrolysis Contributes to Mitotic Chromosome Condensation.

Maeshima K, Matsuda T, Shindo Y, Imamura H, Tamura S, Imai R, Kawakami S, Nagashima R, Soga T, Noji H, Oka K, Nagai T.

Curr Biol. 28 ( 3 ) 444 - 451 2018.02

Research paper (scientific journal), Joint Work, Accepted

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A Transient Rise in Free Mg²⁺ Ions Released from ATP-Mg Hydrolysis Contributes to Mitotic Chromosome Condensation

Maeshima K., Matsuda T., Shindo Y., Imamura H., Tamura S., Imai R., Kawakami S., Nagashima R., Soga T., Noji H., Oka K., Nagai T.

Current Biology (Current Biology)  28 ( 3 ) 444 - 451.e6 2018.02

ISSN  09609822

　View Summary

For cell division, negatively charged chromatin, in which nucleosome fibers (10 nm fibers) are irregularly folded [1–5], must be condensed into chromosomes and segregated. While condensin and other proteins are critical for organizing chromatin into the appropriate chromosome shape [6–17], free divalent cations such as Mg2+ and Ca2+, which condense chromatin or chromosomes in vitro [18–28], have long been considered important, especially for local condensation, because the nucleosome fiber has a net negative charge and is by itself stretched like “beads on a string” by electrostatic repulsion. For further folding, other positively charged factors are required to decrease the charge and repulsion [29]. However, technical limitations to measure intracellular free divalent cations, but not total cations [30], especially Mg2+, have prevented us from elucidating their function. Here, we developed a Förster resonance energy transfer (FRET)-based Mg2+ indicator that monitors free Mg2+ dynamics throughout the cell cycle. By combining this indicator with Ca2+ [31] and adenosine triphosphate (ATP) [32] indicators, we demonstrate that the levels of free Mg2+, but not Ca2+, increase during mitosis. The Mg2+ increase is coupled with a decrease in ATP, which is normally bound to Mg2+ in the cell [33]. ATP inhibited Mg2+-dependent chromatin condensation in vitro. Chelating Mg2+ induced mitotic cell arrest and chromosome decondensation, while ATP reduction had the opposite effect. Our results suggest that ATP-bound Mg2+ is released by ATP hydrolysis and contributes to mitotic chromosome condensation with increased rigidity, suggesting a novel regulatory mechanism for higher-order chromatin organization by the intracellular Mg2+-ATP balance. How the negatively charged long genomic DNA is organized into mitotic chromosome remains unclear. Using a newly developed Mg2+ indicator, Maeshima et al. demonstrate a transient rise in free Mg2+ released from ATP-Mg during mitosis and suggest that the rise contributes to mitotic chromosome condensation by charge neutralization.

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Highly sensitive bioluminescent probe for thiol detection in living cells.

Hemmi M, Ikeda Y, Shindo Y, Nakajima T, Nishiyama S, Oka K, Sato M, Hiruta Y, Citterio D, Suzuki K.

Chem Asian J.2017 (Chemistry - An Asian Journal)  13 ( 6 ) 648 - 655 2018.01

Research paper (scientific journal), Joint Work, Accepted,  ISSN  18614728

　View Summary

The sensitive detection of thiols including glutathione and cysteine is desirable owing to their roles as indispensable biomolecules in maintaining intracellular biological redox homeostasis. Herein, we report the design and synthesis of SEluc-1 (sulfinate ester luciferin), a chemoselective probe exhibiting a ratiometric and turn-on response towards thiols selectively in fluorescence and bioluminescence, respectively. The probe, which was designed based on the “caged” luciferin strategy, displays excellent selectivity, high signal/noise ratio (>240 in the case of bioluminescence), and a biologically relevant limit of detection (LOD, 80 nm for cysteine), which are all desirable traits for a sensitive bioluminescent sensor. SEluc-1 was further applied to fluorescence imaging of thiol activity in living human cervical cancer HeLa cell cultures, and was successfully able to detect fluctuations in thiol concentrations induced by oxidative stress in a bioluminescent assay utilizing African green monkey fibroblast COS-7 cells and human breast adenocarcinoma MCF-7 cells.

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Characterization of calcium transients during early embryogenesis in ascidians Ciona robusta (Ciona intestinalis type A) and Ciona savignyi.

Akahoshi T, Hotta K, Oka K.

Developmental biology. 431 ( 2 ) 205 - 214 2017.11

Research paper (scientific journal), Joint Work, Accepted

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Compartmentalized cGMP Responses of Olfactory Sensory Neurons in Caenorhabditis elegans

Shidara H, Hotta K, Oka K.

The Journal of neuroscience. 37 ( 14 ) 3753 - 3763 2017.04

Research paper (scientific journal), Joint Work, Accepted

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Mitochondrial Mg²⁺ homeostasis decides cellular energy metabolism and vulnerability to stress

Yamanaka R, Tabata S, Shindo Y, Hotta K, Suzuki K, Soga T, Oka K

Scientific Reports 6 ( 30027 )  2016.07

Research paper (scientific journal), Joint Work, Accepted

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An Artificial Reaction Promoter Modulates Mitochondrial Functions via Chemically Promoting Protein Acetylation

Shindo Y, Komatsu H, Hotta K, Ariga K, Oka K

Scientific Reports 6 ( 29224 )  2016.07

Research paper (scientific journal), Joint Work, Accepted

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Altered expression of Mg²⁺ transport proteins during Parkinson's disease-like dopaminergic cell degeneration in PC12 cells

Shindo Y, Yamanaka R, Suzuki K, Hotta K, Oka K

Biochim Biophys Acta 1863 ( 8 ) 1979 - 1984 2016.05

Research paper (scientific journal), Joint Work

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Qualitative and quantitative estimation of comprehensive synaptic connectivity in short- and long-term cultured rat hippocampal neurons with new analytical methods inspired by Scatchard and Hill plots.

Tanamoto R., Shindo Y., Niwano M., Matsumoto Y., Miki N., Hotta K., Oka K.

Biochem Biophys Res Commun. 471 ( 4 ) 486 - 491 2016.03

Research paper (scientific journal), Joint Work

• Access to Document (DOI)

Detection of Temperature Difference in Neuronal Cells.

Tanimoto R., Hiraiwa T., Nakai Y., Shindo Y., <U<Oka K.(/)-#HR, Hiroi N., Funahashi A.

Scientific Reports. 6 ( 22071 )  2016.03

Research paper (scientific journal), Joint Work, Accepted

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Neural depolarization triggers Mg²⁺ influx in rat hippocampal neurons. Neuroscience.

Yamanaka R., Shindo Y., Karube T., Hotta K., Suzuki K., Oka K.

Neuroscience. 310   731 - 741 2015.12

Research paper (scientific journal), Joint Work, Accepted

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Spatiotemporal quantification of subcellular ATP levels in a single HeLa cell during changes in morphology

Suzuki R., Hotta K., Oka K.

Sci Rep. 5 ( 16874 )  2015.11

Research paper (scientific journal), Joint Work, Accepted

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Electrical stimulation of cultured neurons using a simply patterned indium-tin-oxide (ITO) glass electrode.

Tanamoto R., Shindo Y., Miki N., Matsumoto Y., Hotta K., Oka K.

Juournal of Nuroscience Methods. 253   272 - 278 2015.09

Research paper (scientific journal), Joint Work, Accepted

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Intracellular magnesium level determines cell viability in the MPP⁺ model of Parkinson's disease.

Shindo Y., Yamanaka R., Suzuki K., Hotta K., Oka K.

Biochim Biophys Acta. 1853 ( 12 ) 3182 - 3191 2015.08

Research paper (scientific journal), Joint Work, Accepted

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Direction-Specific Adaptation in Neuronal and Behavioral Responses of an Insect Mechanosensory System.

Ogawa H., Oka K.

The Journal of Neuroscience. 35 ( 33 ) 11644 - 11655 2015.08

Research paper (scientific journal), Joint Work

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Evaluation of drug toxicity profiles based on the phenotypes of ascidian Ciona intestinalis.

Mizotani Y., Itoh S., Hotta K., Tashiro E., Oka K.

Biochem Biophys Res Commun. 463 ( 4 ) 656 - 660 2015.08

Research paper (scientific journal), Joint Work, Accepted

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Cysteine residues in Cu,Zn-superoxide dismutase are essential to toxicity in Caenorhabditis elegans model of amyotrophic lateral sclerosis.

Ogawa M., Shidara H., Oka K., Kurosawa M., Nukina N., Furukawa Y.

Biochem Biophys Res Commun. 463 ( 4 ) 1196 - 1202 2015.08

Research paper (scientific journal), Joint Work, Accepted

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Photodegradation of amyloid β and reduction of its cytotoxicity to PC12 cells using porphyrin derivatives.

Hirabayashi A., Shindo Y., Oka K., Takahashi D., Toshima K.

Chem Commun. 50 ( 67 ) 9543 - 9546 2014.08

Research paper (scientific journal), Joint Work, Accepted

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Comprehensive morphological analysis of individual peripheral neuron dendritic arbors in ascidian larvae using the photoconvertible protein kaede.

Yokoyama TD, Hotta K, Oka K.

Dev Dyn. 2014.  2014.07

Research paper (scientific journal), Joint Work, Accepted

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Sexually dimorphic activation of dopaminergic areas depends on affiliation during courtship and pair formation

Iwasaki M, Poulsen TM, Oka K, Hessler NA.

Front Behav Neurosci 8 ( 210 )  2014.06

Research paper (scientific journal), Joint Work, Accepted

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Identification of oscillatory firing neurons associated with locomotion in the earthworm through synapse imaging

Shimoi T., Mizutani K., Kojima D., Kitamura Y., Hotta K., Ogawa H., Oka K.

Neuroscience. 268   149 - 158 2014.05

Research paper (scientific journal), Joint Work, Accepted

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Ubiquinone-Rhodol (UQ-Rh) for Fluorescence Imaging of NAD(P)H through Intracellular Activation

Komatsu H., Shindo Y., Oka K., Hill, J.P., Ariga K

Angew. Chem. 53 ( 15 ) 3993 - 3995 2014.04

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

Design and Synthesis of a FlAsH type Mg²⁺ Fluorescent Probe for Specific Protein Labeling

Fujii T., Shindo Y., Hotta K.,: Citterio D., Nishiyama S., Suzuki K., Oka K.

J Am Chem Soc. 136 ( 6 ) 2374 - 2381 2014.01

Research paper (scientific journal), Joint Work, Accepted

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Singing-related activity in anterior forebrain of male zebra finches reflects courtship motivation for target females

Iwasaki M., Poulsen TM., Oka K., Hessler NA.

PLoS One. 8 ( 11 )  2013.11

Research paper (scientific journal), Joint Work, Accepted

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Crosstalk between Second Messengers Predicts the Motility of the Growth Cone

Kobayashi T., Nagase F., Hotta K., Oka K.

Scientific Reports 3 ( 3118 )  2013.11

Research paper (scientific journal), Joint Work, Accepted

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Development of UV-Excitable Red and Near-Infrared Fluorescent Labels and Their Application for Simultaneous Multicolor Bioimaging by Single-Wavelength Excitation

Mizuno T., Umezawa K., Shindo Y., Citterio D., Oka K., Suzuki K.

Journal of Fluorescence 23 ( 5 ) 1007 - 1018 2013.09

Research paper (scientific journal), Joint Work, Accepted

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A method for selective ablation of neurons in C. elegans using the phototoxic fluorescent protein, KillerRed

Kobayashi J., Shidara H., Morisawa Y., Kawakami M., Tanahashi Y., Hotta K., Oka K.

Neurosci Lett. 548   261 - 264 2013.08

Research paper (scientific journal), Joint Work, Accepted

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Raman Spectroscopic Imaging of the Whole Ciona intestinalis Embryo during Development

Nakamura MJ., Hotta K., Oka K.

PLoS One 8 ( 8 )  2013.08

Research paper (scientific journal), Joint Work, Accepted

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NO/cGMP/PKG signaling pathway induces magnesium release mediated by mitoKATP channel opening in rat hippocampal neurons

Yamanaka R., Shindo Y., Hotta K., Oka K.

FEBS Lett. 587 ( 16 ) 2643 - 2648 2013.08

Research paper (scientific journal), Joint Work, Accepted

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Odorant-induced membrane potential depolarization of AIY interneuron in Caenorhabditis elegans

Shidara H., Kobayashi J., Tanamoto R., Hotta K., and Oka K

Neuroscience Letters 541   199 - 203 2013.04

Research paper (scientific journal), Joint Work, Accepted

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Intracellular activation of acetyl-CoA by an artificial reaction promoter and its fluorescent detection

Komatsu H., Shindo Y., Kawashima S., Yamatsugu K., Oka K, and Kanai M,

Chem. Commun. 2013 ( 49 ) 2876-2878 2013.02

Research paper (scientific journal), Joint Work, Accepted

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Three-dimensional anatomy of the Ciona intestinalis tailbud embryo at single-cell resolution

Nakamura MJ., Terai J., Okubo R., Hotta K., Oka K.

Dev Biol. 372 ( 2 ) 274-84 2012.12

Research paper (scientific journal), Joint Work, Accepted

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Specialized motor-driven dusp1 expression in the song systems of multiple lineages of vocal learning birds

Horita H., Kobayashi M., Liu WC., Oka K., Jarvis ED., Wada K.

PLoS One 7 ( 8 )  2012.08

Research paper (scientific journal), Joint Work, Accepted

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From microscopy data to in silico environments for in vivo-oriented simulations

Hiroi N., Klann M., Iba K., Heras Ciechomski PD., Yamashita S., Tabira A., Okuhara T., Kubojima T., Okada Y., Oka K., Mange R., Unger M., Funahashi A., Koeppl H.

EURASIP J Bioinform Syst Biol. 1 ( 7 )  2012.06

Research paper (scientific journal), Joint Work, Accepted

Physiological environment induces quick response - slow exhaustion reactions

Hiroi N., Lu J., Iba K., Tabira A., Yamashita S., Okada Y., Flamm C., Oka K., Köhler G., Funahashi A.

Front Physiol  2011.09

Research paper (scientific journal), Joint Work, Accepted

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Inhibition of Amyloid β Aggregation and Cytotoxicity by Photodegradation Using a Designed Fullerene Derivative

Ishida Y., Fujii T., Oka K., Takahashi D., Toshima K.

Chem Asian J 6 ( 9 ) 2312 - 2315 2011.09

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

Newly Developed Mg²⁺-Selective Fluorescent Probe Enables Visualization of Mg²⁺ Dynamics in Mitochondria

Shindo Y., Fujii T., Komatsu H., Citterio D., Hotta K., Suzuki K., Oka K.

PLoS ONE 6 ( 8 )  2011.08

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

A Near-Infrared Fluorescent Calcium Probe: a New Tool for　Intracellular Multicolour Ca²⁺ Imaging

Matsui A., Umezawa K., Shindo Y., Fujii T., D Citterio., Oka K. and Suzuki K.

Chem. Commun. 47   10407 - 10409 2011.08

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

Peptidomic analysis of the central nervous system of the protochordate, Ciona intestinalis: homologs and prototypes of vertebrate peptides and novel peptides

Kawada T., Ogasawara M., Sekiguchi T., Aoyama M., Hotta K., Oka K., Satake H.

Endocrinology 152 ( 6 ) 2416 - 2427 2011.06

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

Chromatophore Activity during Natural Pattern Expression by the Squid Sepioteuthis lessoniana: Contributions of Miniature Oscillation

Suzuki M., Kimura T., Ogawa H., Hotta K., Oka K.

PLoS ONE 6 ( 4 )  2011.04

Research paper (scientific journal), Joint Work, Accepted

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細胞内情報伝達を調べるためのマルチカラー蛍光イメージング技術

岡 浩太郎

OPTRONICS 355   126-130 2011

Research paper (scientific journal), Single Work,  ISSN  02869659

マルチカラーイメージングを可能とする蛍光タンパク質プローブの開発

新野祐介、岡 浩太郎

BIOINDUSTRY 28 ( 2 ) 5-10 2011

Research paper (scientific journal), Single Work

Glutamate-induced calcium increase mediates magnesium release from mitochondria in rat hippocampal neurons

Shindo Y, Fujimoto A, Hotta K, Suzuki K, Oka K

J Neurosci Res 88 ( 14 ) 3125-3132 2010.08

Research paper (scientific journal), Joint Work, Accepted

Network structure of projections extending from peripheral neurons in the tunic of ascidian larva

Terakubo HQ, Nakajima Y, Sasakura Y, Horie T, Konno A, Takahashi H, Inaba K, Hotta K, Oka K

Developmental Dynamics 239 ( 8 ) 2278-87 2010.06

Research paper (scientific journal), Single Work

FMRFamide elicits chromatophore expansion and retraction depending on its type and development in the squid, Sepioteuthis lessoniana

Suzuki M, Kimura T, Ogawa H, Hotta K, Oka K

Invert Neurosci 9 ( 3-4 ) 185-93 2010.04

Research paper (scientific journal), Joint Work, Accepted

Blue Fluorescent cGMP sensor for multiparameter fluorescence imaging

Yusuke Niino, Kohji Hotta, and Kotaro Oka

PLoS ONE 5 ( 2 )  2010.02

Research paper (scientific journal), Joint Work, Accepted

Dual FRET イメージング法による細胞内シグナルの同時可視化

新野祐介、堀田耕司、岡浩太郎

生物物理 287 ( 50-1 )  2010.01

Research paper (scientific journal), Single Work, Accepted

Dual FRET イメージング法による細胞内シグナルの同時可視化

新野祐介、堀田耕司、岡 浩太郎

生物物理 287 ( 50-1 )  2010

Research paper (scientific journal), Joint Work

Neural substrate of sound duration discrimination during an auditory sequence in the guinea pig primary auditory cortex

Okazaki S, Kanoh S, Tsukada M, Oka K

Hear Res 259 ( 1-2 ) 107-116 2009.10

Research paper (scientific journal), Joint Work, Accepted

Cell-based in vivo dual imaging probes using genetically expressed tags and chemical contrast agents

Yuki Hasagawa, Aki Nonda, Kietaro Umezawa, Yusuke Niino, Kotaro Oka, Tomohiro Chiba, Sadakazu Aiso, Akihiro Tanimoto, Daniel Citterio and Koji Suzuki

Chem. Commun 27   4040-4042 2009.07

Research paper (scientific journal), Joint Work, Accepted

Simultaneous Live Cell Imaging Using Dual FRET Sensors with a Single Excitation Light

Yusuke Niino, Kohji Hotta, and Kotaro Oka

PLoS ONE 4 ( 6 )  2009.06

Research paper (scientific journal), Joint Work, Accepted

Dextran Coated Cadolinium Phosphate Nanoparticles for Magnetic Resonance Tumor Imaging

Hiroki Hifumi, Seiichi Yamaoka, Akihiro Tanimoto, Tomotaka Akatsu, Yutaka Shindo, Aki Honda, Daniel Citterio, Kotaro Oka, Sachiko Kuribayashi, and Koji Suzuki

Journal of Materials Chemistry 19   6393-6399 2009.06

Research paper (scientific journal), Joint Work, Accepted

Anomalous Exciton Spectra of Laser-Driven Semiconductor Superlattices

Kenta Yashima, Kotaro Oka, Kenichi Hino, Nobuya Maeshima, and Xia Min Tong

Solid State Communications 149 ( 21-22 ) 823-826 2009.06

Research paper (scientific journal), Single Work, Accepted

Network features and pathway analyses of a signal transduction cascade

Ryoji Yanashima, Noriyuki Kitagawa, Yoshiya Matsubara, Robert Weatheritt, Kotaro Oka, Shinicni Kikichi, Masaru Tomita and Shun Ishizaki

Frontiers in Neuroinformatics 3 ( 13 )  2009.05

Research paper (scientific journal), Joint Work, Accepted

Genome-wide searching with base-pairing kernel functions for noncoding RNAs: computational and expression analysis of snoRNA families in Caenorhabditis elegans

Morita K, Saito Y, Sato K, Oka K, Hotta K, Sakakibara Y.

Nucleic Acids Res. 37 ( 3 ) 999-1009 2009.01

Research paper (scientific journal), Joint Work, Accepted

Dextran Coated Gadolinium Phosphate Nanoparticles for Magnetic Resonance Tumor Imaging

Hiroki Hifumi, Seiichi Yamaoka, Akihiro Tanimoto, Tomotaka Akatsu, Yutaka Shindo, Aki Honda, Daniel Citterio, Kotaro Oka, Sachio Kuribayashi and Koji Suzuki*

OURNAL OF MATERIALS CHEMISTRY 19 ( 35 ) 6393-6399 2009

Research paper (scientific journal), Joint Work, Accepted

Nitric Oxide-cGMP Signaling in the Local Circuit of the Cricket Abdominal Nervous System

H. Aonuma, Y. Kitamura, K. Niwa, H. Ogawa,K. Oka

Neuroscience 157 ( 4 ) 749-61 2008.12

Research paper (scientific journal), Joint Work, Accepted

A novel biological role of tachykinins as an up-regulator of oocyte growth: identification of an evolutionary origin of tachykininergic functions in the ovary of the ascidian, Ciona intestinalis.

Aoyama M, Kawada T, Fujie M, Hotta K, Sakai T, Sekiguchi T, Oka K, Satoh N, Satake H

Endocrinology 149 ( 9 ) 4346-4356 2008.05

Research paper (scientific journal), Joint Work, Accepted

Dendritic design inplements algorithm for synaptic extraction of sensory information

Ogawa H., G. I. Cummins., Gwen A. Jacobs and Oka K.

The Journal of Neuroscience 28 ( 18 ) 4592-4603 2008.04

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

Ca²⁺ influx through P2X receptors induces actin cytoskeleton reorganization by the formation of cofilin rods in neurites

Homma H., Niino Y., Hotta Y. and Oka K.

Molecular and Cellular Neuroscience 37   261 - 270 2008.02

Research paper (scientific journal), Single Work, Accepted

• Access to Document (DOI)

Algebraic method for the analysis of signaling crosstalk

Matsubara Y., Kikuchi S., Sugimoto M., Oka K. and Tomita M.

Artificial Life 14 ( 1 ) 81 - 94 2008.01

Research paper (scientific journal), Single Work, Accepted

• Access to Document (DOI)

キンカチョウ音声識別の生物学－社会適応行動の獲得機構－

岡 浩太郎

計測と制御 (社団法人計測自動制御学会)  46   893-897 2007.12

Research paper (scientific journal), Single Work

Flagella facilitate escape of Salmonella from oncotic 1 macropharges

Sano G., Takada Y., Goto S., Maruyama K., Shindo Y., Oka K., Matsui H. and Matsuo K.

Journal of Bacteriology 189 ( 22 ) 8224 - 8232 2007.09

Research paper (scientific journal), Single Work, Accepted

• Access to Document (DOI)

細胞内マグネシウムイオン濃度を測定する蛍光プローブの開発と細胞機能解析への応用

新藤豊、岡浩太郎、小松広和、鈴木孝治

蛋白質・核酸・酵素 52 ( 13 ) 1552 - 1557 2007

Research paper (scientific journal), Joint Work

Neurite level imaging of living PC12 cell with scanning electrochemical / near-field optical / atomic force microscopy

Akio Ueda, Osamu Niwa, Kenichi Maruyama, Yutaka Shindo, Kotaro Oka and Koji Suzuki

Angewandte Chemie 119   8386-8389 2007

Research paper (scientific journal), Single Work, Accepted

Serotonin induces the increase in intracellular Ca²⁺ which enhances neurite outgrowth in PC12 cells via the activation of 5-HT3 receptors and voltage-gated calcium channels

Homma K., Kitamura Y., Ogawa H., Oka K.

Journal of Neuroscience Research 84   316 - 325 2006.05

Research paper (scientific journal), Single Work, Accepted

• Access to Document (DOI)

Change detection and di¡erence detection of tone duration discrimination

Okazaki S., Kanoh S., Takaura K., Tsukada M and Oka K.

Neuro Report 17 ( 4 ) 395 - 399 2006.03

Research paper (scientific journal), Single Work, Accepted

マグネシウム蛍光プローブの設計と応用・Ca²⁺、Mg²⁺マルチ蛍光プローブの開発と多成分同時解析

小松広和、岡浩太郎、鈴木孝治

生物工学会誌 84 ( 5 ) 173 - 175 2006

Research paper (scientific journal), Joint Work

細胞内シグナル伝達系のシミュレーション技法とイメージング技術

菊地進一、松原嘉哉、矢澤和明、山南春奈、冨田勝、岡浩太郎

シミュレーション 25 ( 1 ) 29 - 35 2006

Research paper (scientific journal), Joint Work

Single Molecular Multianalyte (Ca²⁺, Mg²⁺) Fluorescent Probe and Applications to Bioimaging

Komatsu H., Miki T., D. Citterio, Kubota T., Shindo Y., Kitamura Y., Oka K., and Suzuki K.

J of American Chemical Society 127 ( 31 ) 10798 - 10799 2005.07

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

Mitochondria are intracellular magnesium stores: investigation by simultaneous fluorescent imagings in PC12 cells

Kubota T., Shindo Y., Tokuno K., Komatsu K., Ogawa H., Kudo S., Kitamura Y., Suzuki K. and Oka K.

BBA-Molecular Cell Research 1744 ( 1 ) 19 - 28 2005.05

Research paper (scientific journal), Joint Work, Accepted

　View Summary

PC12細胞内Mg動員を、新規蛍光色素KMG-104を用いたCa-Mg同時イメージング法により解析した。細胞内Ca動員を誘導する、カフェイン刺激、細胞内でのケイジド化合物（IP3, Ca）の光解除を行ったところ、細胞内Ca濃度上昇は観察されたが、Mg濃度は変化しなかった。ミトコンドリア脱共役剤FCCPを細胞に添加すると、細胞内で一過的なMgイオン濃度上昇が観測され、これはミトコンドリア膜電位およびミトコンドリアからのCa放出に遅れて生じた。このことから、ミトコンドリアは細胞内でのMg貯蔵器官であると結論した。

• Access to Document (DOI)

Inhibiton of RANKL-induced osteoclastogenesis by (-)-DHMEQ, a novel NF-kB inhibitor, through downregulation of NFATc1.

Takatsuna H., Asagiri M., Kubota T., Oka K., Osada T., Sugiyama C., Saito H., Aoki K., Ohya K., Takayanagi H. and Umezawa K.

J. Bone and Miner. Res. 20 ( 4 ) 653 - 662 2005.04

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

マルチカラーイメージング法による細胞機能の可視化

新野祐介、岡浩太郎

日本レーザ医学会会誌 26   338 - 345 2005

Research paper (scientific journal), Joint Work

Influence of mRNA and protein synthesis inhibitors on the long-term memory acquisition of classically conditioned earthworms.

H.Watanabe, T.Takaya, T.Shimoi, H.Ogawa, Y.Kitamura, and K.Oka

Neurobiol. Learning and Memory 83   151-157 2005

Research paper (scientific journal), Single Work

　View Summary

ミミズの振動ー光の古典的条件付けは古くから研究が行われてきているものの、その成立メカニズムについては不明な点が多い。我々は詳細な行動実験系を構築し、振動ー光の古典的条件付けに与える学習間隔の効果を調べたところ、学習間隔を調整することにより3時間しか維持できない短期記憶と24時間以上維持できる長期記憶の切り替えができることを初めて明らかにした。また学習後１時間以内に転写阻害剤、またはタンパク質合成阻害剤をミミズ腹腔に注射すると、長期記憶形成は阻害されることも示した。

E-Neuron：神経細胞におけるシグナル伝達モデル

菊池進一、関山和秀、松原嘉哉、山岡淳子、竹居光太郎、岡浩太郎、冨田勝

日本神経回路学会誌 12   107 - 112 2005

Research paper (scientific journal), Joint Work

機能が同定された感覚性介在ニューロンにおける樹状突起の能動的特性

小川宏人、岡浩太郎

生物物理 45 ( 4 ) 198 - 202 2005

Research paper (scientific journal), Joint Work

システム生物学－ウェットバイオロジーと計算機科学の接点

岡浩太郎

情報処理学会雑誌 46 ( 3 ) 246-253 2005

Research paper (scientific journal), Single Work

神経とマグネシウム

岡浩太郎

Clinical Calcium 15 ( 11 ) 1-4 2005

Research paper (scientific journal), Single Work

Design and synthesis of high-sensitive and selective fluorescein-derived magnesium fluorescent probes and application to intracellular 3D-Mg²⁺ imaging.

Komatsu H., Iwasawa N., D.Citterio, Suzuki Y., Kubota T., Tokuno K., Kitamura Y., Oka K. and Suzuki K.

J. Am. Chem. Soc. 126 ( 50 ) 16353 - 16360 2004.11

Research paper (scientific journal), Single Work, Accepted

　View Summary

フルオレセインを蛍光団として持つマグネシウムプローブKMG-101, 103, 104を設計・合成し、その特性について調べた。その結果KMG-104は共焦点レーザ顕微鏡で広く用いられているアルゴンレーザで励起することが可能であり、また解離定数が約2 mMであることから、細胞内でのマグネシウムイオン濃度変化を計測するのに至適であることを明らかにした。また実際にこの色素を用いて、PC12細胞のマグネシウム３Dイメージを取得することができた。

• Access to Document (DOI)

機能応答性蛍光プローブの開発とバイオイメージングへの応用　-システム生物学のためのバイオイメージング技術-

岡浩太郎

慶應医学 81 ( 2 ) 79-84 2004.06

Research paper (scientific journal), Single Work

　View Summary

細胞内での生理機能のダイナミクスを追跡することは、定量的な細胞モデルを構築する際には必須である。このような方向を目指した研究として、種々のバイオイメージング技術が開発されてきている。本解説では細胞シミュレーションに代表されるような「システム生物学」に利用できる実験技術について、新規イメージングのためのプローブ開発、新規な顕微鏡技術、観察系に擾乱を与える方法に絞り、解説した。

Directional sensitivity of dendritic calcium responses to wind stimuli in the cricket giant interneuron.

Ogawa H, Baba Y, Oka K.

Neurosci Lett. 358 ( 1 ) 185-188 2004.04

Research paper (scientific journal), Joint Work, Accepted

　View Summary

コオロギ最終腹部神経節の巨大介在神経細胞について、コオロギ周囲の種々の方向から風刺激を与えた際の細胞内カルシウム応答と電位応答の分布を調べた。最大の電位応答を示す風の方向により、細胞内カルシウム応答も最大となったが、その分布は両者で大きく異なった。このことは、シナプス後部での電気活動が局所カルシウム応答を制御していることを示している。

• Access to Document (DOI)

Modulation of motor patterns by sensory feedback during earthworm locomotion.

Mizutani K., Shimoi T., Ogawa H., Kitamura Y., Oka K.

Neurosci Res. 48 ( 4 ) 457 - 462 2004.04

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

Mg-Ca蛍光イメージング

久保田健、岡浩太郎

Clinical Calcium 14 ( 8 ) 1219 - 1222 2004

Research paper (scientific journal), Joint Work

　View Summary

細胞内２価カチオンのうち、特にカルシウムイオンとマグネシウムイオンについてその細胞内挙動を可視化する方法について、我々の研究グループで行っている、新規開発色素による蛍光２重染色方法とマルチカラーイメージング方法について解説した。

ミミズにおける周期的活動（這行行動）を形成するメカニズムの解明

水谷賢史、岡浩太郎

日本バイオメカニズム学会誌 28   18 - 21 2004

Research paper (scientific journal), Joint Work

　View Summary

ミミズは這行により移動する。我々の研究室ではこのミミズの這行運動を解析するために、ミミズの仮想這行状態（神経系だけを単離し、這行に対応する運動神経興奮パターンを誘発させる状態）をin vitro実験系で構築することに成功した。またこの標本を用いて、蛍光色素法および電気生理法を併用することにより、運動パターンを生成する神経回路について新たな知見を得ることができた。

第２高調波発生による細胞イメージング　〜細胞膜電位イメージングを中心に〜

岡浩太郎

化学 59 ( 7 ) 76 - 77 2004

Research paper (scientific journal), Single Work

　View Summary

フェムト秒パルス赤外レーザを利用した顕微鏡技術として、最近第２高調波による生体組織イメージングが注目されている。本解説ではこの第２高調波発生のメカニズムについてまず説明し、その後この方法と細胞膜に適当な蛍光プローブを導入することにより細胞膜電位イメージングが可能であることを、最近の研究を中心に説明した。

Differences of pO2 peaks of a murine fibrosarcoma between carbon-ion and x-ray irradiation.

Fukawa T., Takematsu K., Oka K., Koike S, Ando K., Kobayashi H. and Tanishita K.

J. Radiat. Res. 45 ( 2 ) 303 - 308 2004

Research paper (scientific journal), Single Work, Accepted

• Access to Document (DOI)

分岐管気道モデル内振動流に発生する乱れ

田中学，上田義郎，岡庭貴志，岡浩太郎，谷下一夫

日本機械学会論文集B編 70B ( 696 ) 2057-2064 2004

Research paper (scientific journal), Joint Work

Real-time measurement of nitric oxide using a bio-imaging and an electrochemical technique.

Kitamura Y., Ogawa H. and Oka K.

Talanta 61 ( 5 ) 717 - 724 2003.12

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

Kinetic simulation of signal transduction system in hippocampal long-term potentiation with dynamic modeling of protein phosphatase 2A.

Kikuchi S., Fujimoto K., Kitagawa N., Fuchikawa T., Abe M., Oka K., Takei K., Tomita M.

Neural Netw. 16 ( 9 ) 1389 - 1398 2003.11

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

Identification of two types of synaptic activity in the earthworm nervous system during locomotion.

Mizutani K., Shimoi T., Kitamura Y., Ogawa H., Oka K.

Neuroscience 121 ( 2 ) 473 - 478 2003.10

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

システムバイオロジー研究者育成プログラムの紹介　慶應義塾大学理工学部

岡浩太郎

蛋白質核酸酵素 48 ( 7 ) 829-830 2003.06

Research paper (scientific journal), Single Work

Na⁺/Mg²⁺ transporter acts as a Mg²⁺ buffering mechanism in PC12 cells.

Kubota T., Tokuno K., Nakagawa J., Kitamura Y., Ogawa H., Suzuki Y., Suzuki K., Oka K.

Biochem Biophys Res Commun. 303 ( 1 ) 332 - 336 2003.03

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

マグネシウムイオン蛍光分子プローブ

鈴木祥夫、岡浩太郎、鈴木孝治

和光純薬時報 72 ( 3 ) 2-5 2003

Research paper (scientific journal), Joint Work

Dual responses of tissue partial pressure of oxygen after functional stimulation in rat somatosensory cortex.

K.Masamoto, N.Takizawa, H.Kobayahsi, K.Oka and K.Tanishita

Brain Res. 979 ( 1-2 ) 104-113 2003

Research paper (scientific journal), Joint Work, Accepted

Effect of long-term shear stress exposure on calcium response and morphology of cultured endothelial cells.

Kudo S., Yamaguchi R., Machida K., Ikeda J., #HOka K., and Tanishita K.

JSME Int. J. series C. 46 ( 4 ) 1226 - 1233 2003

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

Direction of action potential propagation influences calcium increases in distal dendrites of the cricket giant interneurons.

Ogawa H., Baba Y., Oka K.

J. Neurobiol. 53 ( 1 ) 44 - 56 2002.10

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

Design and synthesis of Mg²⁺ selective fluoroionophores based on a coumarin derivative and application for Mg²⁺ measurement in a living cell.

Suzuki Y., Komatsu H., Ikeda T., Saito N., Araki S., Citterio D., Hisamoto D., Kitamura Y., Kubota T., Nakagawa J., Oka K., Suzuki K.

Anal Chem. 74 ( 6 ) 1423 - 1428 2002.09

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

Microscopic velocimetry with a scaled up model for evaluateing a flow field over cultured endothelial cells.

Fukushima S., Deguchi T., Kaibara M., Oka K. and Tanishita K.

Trans. ASME J. Biomechanical Engin. 124 ( 2 ) 176 - 179 2002.03

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

Fictive locomotion induced by octopamine in the earthworm.

Mizutani K., Ogawa H., Saito J., Oka K.

J. Exp. Biol. 205 ( 2 ) 265 - 271 2002.01

Research paper (scientific journal), Joint Work, Accepted

Spike-triggered dendritic calcium transients depend on synaptic activity in the cricket giant interneurons.

Ogawa H, Baba Y, Oka K.

J. Neuorbiol. 50 ( 3 ) 234-244 2002

Research paper (scientific journal), Joint Work

Secondary flow augmentation during intermittent oscillatory flow in model human central airways.

G. Tanaka, K.Oka, and K. Tanishita

JSME International Journal Series C 44 ( 4 ) 1041-1050 2001

Research paper (scientific journal), Joint Work

　View Summary

高頻度換気により気道内のガス交換を効率的に行うという試みがなされてきている。我々は間欠振動換気により軌道内ガス拡散が増強されることを明らかにするために、ヒト気道を模擬した分岐管を用いて、高頻度間欠的振動換気のメカニズムを、レーザ流速計を用いて調べた。その結果、stationary periodの最初から管内２次流れの増強が特に気管にで起きることがガス拡散増強を引き起こしていることを明らかにした。

Visualization of nitric oxide production in the earthworm ventral nerve cord.

Kitamura Y, Naganoma Y, Horita H, Tsuji N, Shimizu R, Ogawa H, Oka K

Neurosci Res. 40 ( 2 ) 175-181 2001

Research paper (scientific journal), Joint Work

Serotonin-induced nitric oxide production in the ventral nerve cord of the earthworm, Eisenia fetida.

Kitamura Y, Naganoma Y, Horita H, Ogawa H, Oka K.

Neurosci. Res. 41 ( 2 ) 129-135 2001

Research paper (scientific journal), Joint Work

Native Response of C. elegans Encoded in Its Neuron Network

Y.Funabashi, K. Kawamura, K.Oshio, S.Morita, Y. Osana, E.Akiyama and K.Oka

J. Phys. Soc. Jpn. 70 ( 4 ) 1154-1161 2001

Research paper (scientific journal), Joint Work, Accepted

Does a Randomly Organized Electrical Circuit Function as a Neuronal System?

K.Kawamura, Y.Funabashi, S.Morita, K.Omata, K.Oshio, Y.Osana and K.Oka

Jpn. J. Appl. Phys. 40   2095-2099 2001

Research paper (scientific journal), Joint Work, Accepted

マイクロカプセル化による凍結保存細胞の生存率改善

松本吉史，守永幸弘，氏平政伸，岡浩太郎，谷下一夫

日本機械学会論文集 678 ( 654 ) 580-587 2001

Research paper (scientific journal), Joint Work, Accepted

Oscillatory flow and gas transport through a symmetrical bifurcation.

H.Fujioka, K.Oka and K.Tanishita

J. Biomechanical Engin. 123   145-153 2001

Research paper (scientific journal), Joint Work, Accepted

Geometrical structure of the neural network of caenorhabditis elegans.

S.Morita, K.Oshio, Y.Osana, Y.Funabashi, K.Oka and K. Kawamura

Physica A 298   553-561 2001

Research paper (scientific journal), Joint Work, Accepted

Measurement of surface topography of endothelial cell and wall shear stress distribution on the cell.

S.Fukushima, A.Nagatsu, M.Kaibara, K.Oka and K.Tanishita

JSME International J. C 44 ( 4 ) 972-981 2001

Research paper (scientific journal), Joint Work, Accepted

Design and Application of Novel Fluorescent Indicators of Mg2+

Y.Suzuki, N.Saito, H.Komatsu, D.Citterio, Y.Kitamura, T.Kubota, K.Oka and K.Suzuki

Anal. Sci. 17   1451-1454 2001

Research paper (scientific journal), Joint Work, Accepted

In vivo一酸化窒素（ＮＯ）測定のための同軸型微小電極

北村美一郎，鵜澤智之，駒井豊，小川宏人，瀧澤直定，小林弘祐，谷下一夫，岡浩太郎

生物物理 41 ( 1 ) 32-34 2001

Research paper (scientific journal), Joint Work, Accepted

培養内皮細胞のATP生産能に及ぼす壁せん断応力の影響

工藤奨，山口隆平，岡浩太郎，谷下一夫

日本バイオレオロジー学会誌 (B&R) 15 ( 2 ) 38-39 2001

Research paper (scientific journal), Joint Work

Dendritic calcium accumulation regulates wind sensitivity via short-term depression at cercal sensory-to-giant interneuron synapses in the cricket.

H.Ogawa, Y.Baba and K.Oka

J. Neurobiol. 46   301-313 2001

Research paper (scientific journal), Joint Work

　View Summary

コオロギ最終腹部神経節にある巨大介在神経細胞について、その神経細胞機能を明らかにするためにカルシウムイメージングを行った。感覚神経細胞からの入力頻度に応じて介在神経細胞樹状突起でのカルシウム濃度増加は増加し、それに伴い興奮電位生成は減少した。このことはシナプス後部でのカルシウム濃度変化が神経興奮を短期間抑制するという新規なシナプス可塑性メカニズムの存在を示唆している。

Nitric oxide generation around buccal ganglia accompanying feeding behavior in the pond snail, Lymnaea stagnalis.

S.Kobayashi, H.Sadamoto, H.Ogawa, Y.Kitamura, K.Oka, K.Tanishita and E.Ito

Neurosci. Res. 38 ( 1 ) 27-34 2000

Research paper (scientific journal), Joint Work, Accepted

Spike-dependent calcium　influx in dendrites of the cricket giant interneuron.

H.Ogawa, Y.Baba and K.Oka

J. Neurobiol. 44 ( 1 ) 45-56 2000

Research paper (scientific journal), Joint Work, Accepted

Shear-stress effect on mitochondorial membrane potential and albumin uptake in cultured endothelial cells

S.Kudo, R.Morigaki, J.Saito, M.Ikeda, K.Oka and K.Tanishita

Biochem. Biophys. Res. Commun. 270   616-621 2000

Research paper (scientific journal), Joint Work, Accepted

Microcoaxial electrode for in vivo nitric oxide measurement.

Y.Kitamua, T.Uzawa, K.Oka, Y. Komai, H. Ogawa, N.Takizawa, H.Kobayashi and K.Tanishita

Anal. Chem. 72 ( 13 ) 2957-2962 2000

Research paper (scientific journal), Joint Work, Accepted

剥離流れ場における培養内皮細胞の高分子物質取り込みと形態変化

工藤奨、佐藤正志、町田和敏、山口隆平、黒川原佳、松澤照男、池田満里子、岡浩太郎、谷下一夫

日本機械学会論文集（B編 65B ( 639 ) 3705-3712 1999

Research paper (scientific journal), Joint Work

　View Summary

はく離流れ場における内皮細胞形態と物質取り込みについて、段差のあるモデル流路にウシ大動脈由来血管内皮細胞を播種した実験系で調べた。せん断応力が大きくかつせん断勾配が小さい領域では内皮細胞は伸長し、流れ方向への細胞配向が見られ、アルブミンの取込みは少なかった。一方、低せん断かつせん断応力勾配の大きい部位では、内皮細胞の面積は大きく、密度は減少し、アルブミン取り込みの増大が観察された。

Optical monitoring of the neural activity evoked by mechanical stimulaion in the earthworm nervous system with a fluorescent dye, FM1-43

R.Shimizu, K.Oka, H.Ogawa, K.Suzuki, J. Saito, K.Mizutani and K.Tanishita

Neurosci. Lett. 268   159-162 1999

Research paper (scientific journal), Joint Work, Accepted

Relationship between energy-dependent macromolecule uptake and transport granules in the endothelial cells affected by wall shear stress.

S.Kudo, K.Ikezawa, S.Matsumura, M.Ikeda, K.Oka and K.Tanishita

JSME International J. 42 ( 3 ) 706-714 1999

Research paper (scientific journal), Joint Work, Accepted

Dendritic Ca2+ transient increase evoked by　wind stimulus in the cricket giant interneuron.

H.Ogawa, Y. Baba and K.Oka

Neurosci. Lett. 275   61-64 1999

Research paper (scientific journal), Joint Work, Accepted

Spatial and temporal variation of secondary flow during oscillatory flow in model human airways.

G.Tanaka, T.Ogata, K.Oka and K.Tanishita

J. Biomech. Eng. 121 ( 6 ) 565-573 1999

Research paper (scientific journal), Joint Work, Accepted

光学測定による細胞機能の可視化　細胞機能をリアルタイムに調べる方法

岡浩太郎，小川宏人

画像ラボ 10 ( 8 ) 5-9 1999

Research paper (scientific journal), Joint Work

内皮細胞近傍の流れの計測

福島修一郎，出口隆明，貝原真，岡浩太郎，谷下一夫

日本バイオレオロジー学会誌（B&R） 12 ( 4 ) 226-233 1998

Research paper (scientific journal), Single Work

培養内皮細胞の高分子物質取り込みに及ぼす壁せん断応力の影響

工藤奨，池澤憲司，松村伸治，池田満里子，岡浩太郎，谷下一夫

日本機械学会論文集（B編） 64B ( 618 ) 367-374 1998

Research paper (scientific journal), Joint Work, Accepted

　View Summary

ブタ培養血管内皮細胞に流れ負荷した時のアルブミン取り込みを，蛍光ラベリングしたアルブミンと共焦点レーザ顕微鏡を併用して調べた。10dyn/cm2程度の低せん断応力の負荷は細胞内へのアルブミンを取り込みを亢進させるが，それより高せん断では逆に取り込みは抑制されるという新知見を得た。

壁せん断応力による培養内皮細胞の代謝依存的な高分子物質取り込み変化と細胞内顆粒との関係

工藤奨，池澤憲司，松村伸治，池田満里子，岡浩太郎，谷下一夫

日本機械学会論文集（B編） 64B ( 623 ) 2123-2131 1998

Research paper (scientific journal), Joint Work, Accepted

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培養内皮細胞へのアルブミン取り込みについて，特にその輸送ユニットである細胞内顆粒に着目して解析した。細胞内顆粒の輸送はエネルギー代謝に依存することを明らかにした。また細胞内への取り込みにはこの細胞内顆粒の個数または大きさの変化が影響を与えるが，特に個数変化が顕著に変わることを明らかにした。

凍結保存状態の評価を目的とした赤血球懸濁液における有効熱物性値の測定

島本敦介，氏平政伸，鈴木雅之，岡浩太郎，谷下一夫

日本機械学会論文集（B編） 64B ( 625 ) 3068-3076 1998

Research paper (scientific journal), Joint Work, Accepted

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様々な凍結条件で赤血球懸濁液を凍結させ，そのさいの有効熱物性値と凍結状態との関連を調べた。細胞内外の氷晶形成量の減少を有効温度伝導率の低下としてとらえることができた。また走査型電子顕微鏡で観察した細胞内凍結の状態は有効温度伝導率変化としてとらえられることが明らかにした。

各種蛍光イメージング法を用いたミミズ神経系の解析

小川宏人，岡浩太郎

バイオイメージング 7 ( 1 ) 1-9 1998

Research paper (scientific journal), Single Work

共焦点レーザ顕微鏡による生体内物質輸送解析

岡浩太郎

第２回センシングフォトニクス部会講演会-フォトバイオセンシング-資料 PG0009   43-49 1997

Research paper (conference, symposium, etc.), Single Work

磁気的ターゲッティングのための磁性微粒子含有リポソームの作製と特性評価

常盤幸恵、笠毛邦弘、岡浩太郎、太田英二、佐藤徹哉

DDS 12   43-48 1997

Research paper (scientific journal), Joint Work, Accepted

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磁性微粒子を含有するリポソームを開発し，ブタ血管内皮培養細胞への取り込みを共焦点レーザ顕微鏡を用いて調べた。磁場が存在する部位では存在しない部位と比べて有為にリポソームの取り込みは増加した。このことは，今回開発したリポソームをドラッグデリバリーに利用可能であることを示す。

ガス吸収壁面をもつ円管内振動流における軸方向ガス輸送の数値解析

藤岡秀樹，岡浩太郎，谷下一夫

日本機械学会論文集（C編） 63C ( 607 ) 686-692 1997

Research paper (scientific journal), Joint Work, Accepted

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壁面においてガス吸収をすることを仮定した直円管または分岐管におけるガス輸送の様子を数値解析したところ，ガス輸送が最大200倍程度まで亢進することを明らかにした。これは気道壁内へガスが拡散するのに要する時間とガス移流の周期が一致する条件で最大となった。

非対称気道ネットワークモデル内振動流における局所ガス輸送効率の評価

田中学，伊藤仁，岡浩太郎，谷下一夫

日本機械学会論文集（B編） 63B ( 610 ) 1946-1955 1997

Research paper (scientific journal), Joint Work, Accepted

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複数の非対称分岐管からなる気道ガスモデルを用いて，正弦波振動流における局所ガス輸送効率を測定したところ，局所的な流れの状態に依存して局所ガス輸送効率は変化し，また軸方向・各気道間で顕著な差があることが明らかになった。

ミミズgiant fiberにおけるCa2+波

小川宏人、岡浩太郎

生体の科学 47 ( 2 ) 140-145 1996

Research paper (scientific journal), Joint Work

Dendritic Ca2+ response in cercal sensory interneuron of cricket

H.Ogawa, Y.Baba, K.Oka

Neurosci. Lett. 219   21-24 1996

Research paper (scientific journal), Joint Work, Accepted

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コオロギの最終腹部神経節内に存在する巨大介在神経細胞にカルシウム濃度感受性色素を注入し，感覚神経細胞を刺激した際の細胞内カルシウム動員を調べた。感覚神経細胞刺激により巨大介在神経細胞内のカルシウム濃度は不均一に増大した。

Physiological basis of earthworm ventral nerve cord. I. Heterogeneity of cellular mechanisms underlying calcium mobilization

H.Ogawa and K.Oka

Bioimages 4 ( 4 ) 137-147 1996

Research paper (scientific journal), Joint Work, Accepted

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ミミズ巨大軸索内にカルシウム濃度感受性色素を注入し，高濃度KCl，カフェインまたは直接的な電気刺激に伴う細胞内カルシウム動員を調べた。ミミズ巨大軸索には高等脊椎動物神経系と同様な細胞内カルシウム動員機構が存在することを明らかにした。

Physiological basis of earthworm ventral nerve cord. II. Glutamate receptor subtypes on the median giant fiber

K.Oka and H.Ogawa

Bioimages 4 ( 4 ) 149-156 1996

Research paper (scientific journal), Joint Work, Accepted

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ミミズ腹髄神経節をカルシウム濃度感受性色素または膜電位感受性色素で染色し，グルタミン酸とその誘導体で刺激した時の応答を光学的に調べた。グルタミン酸とその誘導体はミミズ巨大軸索に顕著なカルシウム動員をひき起こした。また腹髄神経節の神経細胞はtrans-ACPD以外の総ての薬物刺激に脱分極した。これらのことから，ミミズ腹髄神経節には高等脊椎動物と同様なグルタミン酸受容体が存在することが分った。

レーザー共焦点顕微鏡による生体内物質輸送解析

岡浩太郎、谷下一夫

日本レーザー医学会誌 16 ( 4 ) 33-39 1995

Research paper (scientific journal), Joint Work

β-アミロイドタンパク質によって誘導されるアルツハイマー型のカリウムチャネル異常

伊藤悦朗、岡浩太郎

実験医学 13 ( 3 ) 71-73 1995

Research paper (scientific journal), Joint Work

T字迷路学習

岡浩太郎

生体の科学 45 ( 5 ) 618-619 1994.10

Research paper (scientific journal), Single Work

Calcium wave propagation in the earthworm giant axon

H.Ogawa, K.Oka, S.Fujita

Neuroscience Letters 179   45-49 1994

Research paper (scientific journal), Joint Work, Accepted

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ミミズ膜髄巨大軸索にカルシウム濃度感受性色素カルシウムグリーン１を注入し，外部電気刺激した場合の細胞内カルシウム応答を調べた。電気刺激に伴い，軸索内部をカルシウム波が伝搬することが明らかになった。

Molecular and biophysical steps in the storage of associative memory. Molecular basis of ion channels and receptors involved in nerve ex- citation, synaptic transmission and muscle contraction nd muscle contraction

D.L.Alkon, C.Collin, E.Ito, C.-J.Lee, T.J.Nelson, K.Oka, M.Sakakibara, B.G.Schreurs, T.Yoshioka

Annals of The New York Academy of Sciences 707   500-504 1994

Research paper (scientific journal), Joint Work, Accepted

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ウミウシ光受容細胞では光と振動の学習成立に伴い，カリウムコンダクタンスの減少が起きる。またこのコンダクタンス減少にはＧ蛋白質が関 与していることが明らかになってきた。

Internal Ca２＋ mobilization is altered in fibroblasts from patients with Alzheimers disease

E.Ito, K.Oka, R.Etcheberrigary, T.J.Nelson, D.L.McPhie, B.Tofel-Grehl, G.E.Gibson, D.L.Alkon

Proceedings of National Academy of Science USA 91   534-538 1994

Research paper (scientific journal), Joint Work, Accepted

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アルツハイマー患者由来の繊維芽細胞にカルシウムイメージング法を適用し，ボンベシンで細胞を刺激した場合のカルシウム動員を調べたところ，細胞内カルシウムストアからのカルシウム動員が健常者由来の細胞と異なることが明らかになった。

Intracellular calcium signals are enhanced for days after Pavlovian conditioning

E.Ito, K.Oka, C.Collin, B.G.Schreurs, M.Sakakibara, D.L.Alkon

J. Neurochem. 62 ( 4 ) 1337-1344 1994

Research paper (scientific journal), Joint Work, Accepted

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学習，未学習，ランダム学習を行なった３種類のウミウシの光受容細胞にカルシウムイメージングを試みたところ，学習が成立したウミウシでは細胞内カルシウム上昇が他の２種類と比べ て長く続くことを明らかにした。

Glutamate-induced deporalization in earthworm ventral nerve cord

K.Oka, H.Ogawa, S.Fujita

Neuroscience Letters 179   41-44 1994

Research paper (scientific journal), Joint Work, Accepted

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ミミズ腹髄神経節を膜電位感受性色素ＲＨ４１４で染色し，蛍光顕微鏡と共焦点レーザ顕微鏡を利用して膜電位イメージングを行ない，グルタミン酸に対する応答を調べた。

連合学習の分子メカニズム　-ウミウシを用いた研究-

井上宏子、岡浩太郎、榊原学、吉岡亨

細胞工学 12 ( 7 ) 506-511 1993

Research paper (scientific journal), Joint Work

New implications of memory mechanisms for Alzheimer's disease

R.Etcheberrigary, E.Ito, K.Oka, B.Tofel- Grehl, G.E.Gibson, D.L.Alkon

Neuroscience Research. Communications 13 ( Supplement 1 ) S7-S10 1993

Research paper (scientific journal), Joint Work, Accepted

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アルツハイマー患者，老齢者，健常者からのヒト繊維芽細胞についてパッチクランプ法を適用したところ，113ｐＳのコンダクタンスを持つカリウムチャネルがアルツハイマー患者由来の繊維芽細胞には欠如していることがわかった。

Potassium channel dysfunction infibroblasts identifies patients with Alzheimer disease

R.Etcheberrigary, E.Ito, K.Oka, B.Tofel- Grehl, G.E.Gibson, D.L.Alkon

Proceedings of National Academy of Science USA 90   8209-8213 1993

Research paper (scientific journal), Joint Work, Accepted

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113 ｐＳのコンダクタンスを持つカリウムチャネルがアルツハイマー患者由来の繊維芽細胞には欠如していることがわかった。そこで繊維芽細胞にカルシウム感受性色素をFura－２をロードして，高濃度カリウム刺激を行なったところ，老齢者，健常者からは顕著な細胞内カルシウム濃度の増大が観察できたものの，アルツハイマー患者由来の細胞ではカルシウム濃度増大は起 きなかった。

Long-term transformation of an in-hibitory into an excitatory GABAergic synaptic response

D.L.Alkon, J.V.Sanchez-Andres, E.Ito, K.Oka, T.Yoshioka, C.Collin

Proceedings of National Academy of Science USA 89   11862-11866 1992

Research paper (scientific journal), Joint Work, Accepted

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振動を感受する有毛細胞が光受容神経細胞上に作っているシナプスの可塑性により，ウミウシの連合学習が成立していることが明らかになってきた。そこで光受容細胞にカルシウム濃度感受性色素を注入し，学習前後での細胞内カルシウムの挙動を調べたところ，学習が成立した後では有毛細胞からの神経伝達物質γ－アミノ酪酸により細胞内カルシウム濃度は上昇し，その上昇は学習しないものよりも長期間維持された。

The role of calcium in prolonged modification of a GABAergic synapse

C.Collin, E.Ito, K.Oka, T.Yoshioka, J.V.Sanchez-Andres, L.D.Mantzel, D.L.Alkon

Journal of Physiology (Paris) 86   139-145 1992

Research paper (scientific journal), Joint Work, Accepted

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海産無脊椎動物であるウミウシは正の走光性を示すが，振動と光の組み合わせ学習を行なわせた後では負の走光性に転じる。このメカニズムは振動を感受する有毛細胞が光受容神経細胞が上に作っているシナプスの可塑性と関連があるものと思われる。そこでこのシナプス部位にガラス微小電極法を適用したところ，学習前後で抑制型シナプスが興奮性に転じていることを明らかにした。

Surface charge density estimation of Vigna mungo protoplasts using a fluorescent dye, 9-aminoacridine

K.Oka, H.Ikeshima, H.Ishikawa, E.Ohta, M. Sakata

Plant and Cell Physiology 29 ( 5 ) 771-775 1988

Research paper (scientific journal), Joint Work, Accepted

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蛍光色素9-aminoacridine は細胞膜表面の負電荷により細胞近傍で凝集体を形成し蛍光クエンチすることが知られている。この蛍光クエンチ法を利用して，モヤシマメ胚軸から単離したプ ロトプラストの表面電荷密度を測定し，カルシウムが細胞膜電荷に与える影響を明らかにした。

Membrane potential measurement of protoplasts isolated from Vigna m- ungo hypocotyl using a fluorescent probe, diS-C３-(5)

K.Oka, S.Naitou, M.Yoshida, H.Ishikawa, E.Ohta, M.Sakata

Plant and Cell Physiology 28 ( 5 ) 843-849 1987

Research paper (scientific journal), Joint Work, Accepted

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モヤシマメ胚軸より単離したプロトプラストに蛍光色素法と脂溶性カチオン分配法を適用し，静止膜電位に与えるカルシウムイオンの効果を調べた。

Effects of external Ca２＋ on K＋ pemeability of the elongating region of mung bean roots under high KC1 stress

K.Oka, H.Ishikawa, E.Ohta, M.Sakata

Plant and Cell Physiology 28 ( 4 ) 581-586 1987

Research paper (scientific journal), Joint Work, Accepted

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モヤシマメを高濃度塩ストレス環境に置くと，細胞内からカリウムイオンの放出が生じることを，アイソトープ法と電気生理実験により明らかにした。またこのカリウムイオン放出は細胞外液にカルシウムイオンを添加することにより停止させることが可能であった。