Details of a Researcher

Papers - Oka, Kotaro

Division display 1 - 20 of about 178 ／ All the affair displays >>

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

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.

Access to Document (DOI)

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

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.

Access to Document (DOI)

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

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.

Access to Document (DOI)

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

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.

Access to Document (DOI)

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

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.

Access to Document (DOI)

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

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.

Access to Document (DOI)

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

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.

Access to Document (DOI)

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

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.

Access to Document (DOI)

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

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.

Access to Document (DOI)

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

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.

Access to Document (DOI)

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

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.

Access to Document (DOI)

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

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.

Access to Document (DOI)

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

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.

Access to Document (DOI)

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

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+

Access to Document (DOI)

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

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.

Access to Document (DOI)

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

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.

Access to Document (DOI)

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

Access to Document (DOI)

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

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

Access to Document (DOI)

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

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.

Access to Document (DOI)

　 Previous page - Next page 　