Performance information

• Understanding disorders of the human nervous system: How fish models reveal disease mechanisms from single molecules to behavior (part 2).　　　　　　　　　　　　　　　
  Christina Lillesaar; William Norton; Daniel Liedtke; Sachiko Tsuda
  Development, growth & differentiation, Volume：67, Number：1, First page：4, Last page：5, Jan. 2025, ［Domestic magazine］
  The usefulness of zebrafish for understanding the human nervous system is exemplified by the articles in part 1. The virtual special issue part 2 not only covers more work using this well-established species, but also highlights that other fish species may serve as alternative or more appropriate models, due to unique biological or evolutionary characteristics, to explore genetic and molecular mechanisms of neurological and psychiatric disorders.
  English, Scientific journal
  DOI：https://doi.org/10.1111/dgd.12951
  DOI ID：10.1111/dgd.12951, PubMed ID：39854022
• GPR139 agonist and antagonist differentially regulate retrieval and consolidation of fear memory in the zebrafish.　　　　　　　　　　　　　　　
  Nisa Roy; Satoshi Ogawa; Sachiko Tsuda; Ishwar S Parhar
  Frontiers in neuroscience, Volume：18, First page：1461148, Last page：1461148, 2024, [Reviewed], ［International magazine］
  G protein-coupled receptor 139 (GPR139), a highly conserved orphan receptor, is predominantly expressed in the habenula of vertebrate species. Habenula is an ancient epithalamic structure, which is critical to comprehending adaptive behaviors in vertebrates. We have previously demonstrated the role of GPR139 agonists in fear-associated decision-making processes in zebrafish. However, how GPR139 signaling in the habenula modulates such adaptive behavioral responses remains unsolved. Fish centrally administered with a synthetic antagonist for human GPR139 (NCRW0005-F05) exhibited significant suppression of odorant cue (alarm substance, AS)-induced fear learning in the conditioned place avoidance paradigm. On the other hand, co-treatment with a GPR139 antagonist and a synthetic agonist for human GPR139 (JNJ-63533054) interrupted the fear conditioning process by significantly reducing locomotion during post-conditioning. Calcium imaging of acute brain slices showed a significant increase in peak amplitude of calcium transients in the habenula upon bath application of either a GPR139 antagonist or agonist. Furthermore, KCl-evoked calcium transients were reduced by the GPR139 antagonist and co-treatment of the GPR139 antagonist-agonist. These results suggest that the GPR139 antagonist did not block the inhibitory action of the GPR139 agonist in the decision-making process during the fear-retrieval phase; however, solitarily, it functions in governing the fear consolidation process via activation of the ventral habenula neurons in zebrafish.
  English, Scientific journal
  DOI：https://doi.org/10.3389/fnins.2024.1461148
  DOI ID：10.3389/fnins.2024.1461148, PubMed ID：39717703, PubMed Central ID：PMC11665214
• The effects of paroxetine-induced transient apoptosis and brain remodeling on social behavior in developing zebrafish
  Tomomi Sato; Kaito Saito; Tsubasa Oyu; Sachiko Tsuda; Tomohiro Kurisaki; Takeshi Kajihara; Masabumi Nagashima
  bioRxiv, Nov. 2023
  Abstract
  
  Autism spectrum disorder (ASD) is a neurodevelopmental condition caused by various genetic and environmental factors. This disorder has the cardinal symptoms including impaired social behavior involving the amygdala. Antidepressants such as paroxetine in early pregnancy increase the risk of ASD in offspring. However, a comprehensive picture of the underlying pathogenic mechanisms remains elusive. Here, we demonstrate that early exposure of zebrafish embryos to paroxetine suppresses neurogenesis in the optic tectum and the dorsal telencephalon which corresponds to the human amygdala. Paroxetine-treated embryos exhibit impaired growth, with small heads and short body lengths resulting from transient apoptosis. This is reminiscent of the early-onset fetal growth restriction (FGR) associated with ASD. Interestingly, the suppressed neurogenesis in the small heads was found to be restored after the cessation of paroxetine. This was accompanied by extended retinotectal projections, suggesting brain-preferential remodeling. Finally, the paroxetine-treated fish exhibited impaired social behavior, further supporting the correspondence with ASD. Our findings offer new insights into the early neurodevelopmental etiology of ASD.
  Cold Spring Harbor Laboratory
  DOI：https://doi.org/10.1101/2023.11.10.566506
  DOI ID：10.1101/2023.11.10.566506
• Understanding disorders of the human nervous system: How fish models reveal disease mechanisms from single molecules to behavior (part 1).　　　　　　　　　　　　　　　
  Christina Lillesaar; William Norton; Daniel Liedtke; Sachiko Tsuda
  Development, growth & differentiation, Volume：65, Number：8, First page：432, Last page：433, Oct. 2023, ［Domestic magazine］
  English
  DOI：https://doi.org/10.1111/dgd.12894
  DOI ID：10.1111/dgd.12894, PubMed ID：37881022
• In vivo long-term voltage imaging by genetically encoded voltage indicator reveals spatiotemporal dynamics of neuronal populations during development
  Asuka Shiraishi; Ayane Hayashi; Narumi Fukuda; Mari Hishinuma; Hiroaki Miyazawa; Sachiko Tsuda
  bioRxiv, May 2023, [Last, Corresponding]
  Abstract
  
  A central question in brain development lies in how individual neurons emerge and organize communities to acquire various functions. Voltage imaging provides unique approaches to addressing this by enabling simultaneous, non-invasive, in vivo recording of voltage dynamics from a population of cells. Recently, genetically encoded voltage indicators (GEVIs) facilitate cell-type specific imaging of voltage dynamics. However, it has not been applied to brain development. Here, we applied ArcLight, a GEVI utilizing voltage-sensitive domain, to zebrafish and established experimental approaches for analyzing voltage and morphology of neuron populations during development, focusing on the spinal cord and cerebellum. We initially demonstrated that Arclight was widely distributed in the neural tissues. With voltage imaging, we successfully visualized the coordinated, spontaneous activity of spinal cord neurons in their early stage of development at a high spatiotemporal resolution, at subcellular and population levels. Hyperpolarization and subthreshold signals were also detected. Finally, long-term voltage imaging during development revealed the process of changes in voltage dynamics in neuron populations, accompanied by axonal outgrowth. Voltage imaging could greatly contribute to our understanding of the functional organization of the nervous system during development.
  Cold Spring Harbor Laboratory
  DOI：https://doi.org/10.1101/2023.05.25.540669
  DOI ID：10.1101/2023.05.25.540669
• In vivo wide-field voltage imaging in zebrafish with voltage-sensitive dye and genetically encoded voltage indicator.　　　　　　　　　　　　　　　
  Kanae Hiyoshi; Asuka Shiraishi; Narumi Fukuda; Sachiko Tsuda
  Development, growth & differentiation, Aug. 2021, [Reviewed], [Last, Corresponding], ［Domestic magazine］
  The brain consists of neural circuits, which are assemblies of various neuron types. For understanding how the brain works, it is essential to identify the functions of each type of neuron and neuronal circuits. Recent advances in our understanding of brain function and its development have been achieved using light to detect neuronal activity. Optical measurement of membrane potentials through voltage imaging is a desirable approach, enabling fast, direct, and simultaneous detection of membrane potentials in a population of neurons. Its high speed and directness can help detect synaptic and action potentials and hyperpolarization, which encode critical information for brain function. Here, we describe in vivo voltage imaging procedures that we have recently established using zebrafish, a powerful animal model in developmental biology and neuroscience. By applying two types of voltage sensors, voltage-sensitive dyes (VSDs, Di-4-ANEPPS) and genetically encoded voltage indicators (GEVIs, ASAP1), spatiotemporal dynamics of voltage signals can be detected in the whole cerebellum and spinal cord in awake fish at single-cell and neuronal population levels. Combining this method with other approaches, such as optogenetics, behavioral analysis, and electrophysiology would facilitate a deeper understanding of the network dynamics of the brain circuitry and its development.
  English, Scientific journal
  DOI：https://doi.org/10.1111/dgd.12744
  DOI ID：10.1111/dgd.12744, PubMed ID：34411280
• Two-Photon Laser Ablation and In Vivo Wide-Field Imaging of Inferior Olive Neurons Revealed the Recovery of Olivocerebellar Circuits in Zebrafish.　　　　　　　　　　　　　　　
  Kanae Hiyoshi; Kaito Saito; Narumi Fukuda; Takahisa Matsuzaki; Hiroshi Y Yoshikawa; Sachiko Tsuda
  International journal of environmental research and public health, Volume：18, Number：16, Aug. 2021, [Reviewed], [Invited], [Last, Corresponding], ［International magazine］
  The cerebellum, a brain region with a high degree of plasticity, is pivotal in motor control, learning, and cognition. The cerebellar reserve is the capacity of the cerebellum to respond and adapt to various disorders via resilience and reversibility. Although structural and functional recovery has been reported in mammals and has attracted attention regarding treatments for cerebellar dysfunction, such as spinocerebellar degeneration, the regulatory mechanisms of the cerebellar reserve are largely unidentified, particularly at the circuit level. Herein, we established an optical approach using zebrafish, an ideal vertebrate model in optical techniques, neuroscience, and developmental biology. By combining two-photon laser ablation of the inferior olive (IO) and long-term non-invasive imaging of "the whole brain" at a single-cell resolution, we succeeded in visualization of the morphological changes occurring in the IO neuron population and showed at a single-cell level that structural remodeling of the olivocerebellar circuit occurred in a relatively short period. This system, in combination with various functional analyses, represents a novel and powerful approach for uncovering the mechanisms of the cerebellar reserve, and highlights the potential of the zebrafish model to elucidate the organizing principles of neuronal circuits and their homeostasis in health and disease.
  English, Scientific journal
  DOI：https://doi.org/10.3390/ijerph18168357
  DOI ID：10.3390/ijerph18168357, PubMed ID：34444107, PubMed Central ID：PMC8391264
• Involvement of Oct4-type transcription factor Pou5f3 in posterior spinal cord formation in zebrafish embryos.　　　　　　　　　　　　　　　
  Tatsuya Yuikawa; Masaaki Ikeda; Sachiko Tsuda; Shinji Saito; Kyo Yamasu
  Development, growth & differentiation, Volume：63, Number：6, First page：306, Last page：322, Aug. 2021, [Reviewed], ［Domestic magazine］
  In vertebrate embryogenesis, elongation of the posterior body is driven by de novo production of the axial and paraxial mesoderm as well as the neural tube at the posterior end. This process is presumed to depend on the stem cell-like population in the tail bud region, but the details of the gene regulatory network involved are unknown. Previous studies suggested the involvement of pou5f3, an Oct4-type POU gene in zebrafish, in axial elongation. In the present study, we first found that pou5f3 is expressed mainly in the dorsal region of the tail bud immediately after gastrulation, and that this expression is restricted to the posterior-most region of the elongating neural tube during somitogenesis. This pou5f3 expression was complementary to the broad expression of sox3 in the neural tube, and formed a sharp boundary with specific expression of tbxta (orthologue of mammalian T/Brachyury) in the tail bud, implicating pou5f3 in the specification of tail bud-derived cells toward neural differentiation in the spinal cord. When pou5f3 was functionally impaired after gastrulation by induction of a dominant-interfering pou5f3 mutant gene (en-pou5f3), trunk and tail elongation were markedly disturbed at distinct positions along the axis depending on the stage. This finding showed involvement of pou5f3 in de novo generation of the body from the tail bud. Conditional functional abrogation also showed that pou5f3 downregulates mesoderm-forming genes but promotes neural development by activating neurogenesis genes around the tail bud. These results suggest that pou5f3 is involved in formation of the posterior spinal cord.
  English, Scientific journal
  DOI：https://doi.org/10.1111/dgd.12742
  DOI ID：10.1111/dgd.12742, PubMed ID：34331767
• A globin-family protein, Cytoglobin 1, is involved in the development of neural crest-derived tissues and organs in zebrafish.　　　　　　　　　　　　　　　
  Kazuki Takahashi; Yuki Ito; Mami Yoshimura; Masataka Nikaido; Tatsuya Yuikawa; Akinori Kawamura; Sachiko Tsuda; Daichi Kage; Kyo Yamasu
  Developmental biology, Volume：472, First page：1, Last page：17, Apr. 2021, [Reviewed], ［International magazine］
  The zebrafish is an excellent model animal that is amenable to forward genetics approaches. To uncover unknown developmental regulatory mechanisms in vertebrates, we conducted chemical mutagenesis screening and identified a novel mutation, kanazutsi (kzt). This mutation is recessive, and its homozygotes are embryonic lethal. Mutant embryos suffered from a variety of morphological defects, such as head flattening, pericardial edema, circulation defects, disrupted patterns of melanophore distribution, dwarf eyes, a defective jaw, and extensive apoptosis in the head, which indicates that the main affected tissues are derived from neural crest cells (NCCs). The expression of tissue-specific markers in kzt mutants showed that the early specification of NCCs was normal, but their later differentiation was severely affected. The mutation was mapped to chromosome 3 by linkage analyses, near cytoglobin 1 (cygb1), the product of which is a globin-family respiratory protein. cygb1 expression was activated during somitogenesis in somites and cranial NCCs in wild-type embryos but was significantly downregulated in mutant embryos, despite the normal primary structure of the gene product. The kzt mutation was phenocopied by cygb1 knockdown with low-dose morpholino oligos and was partially rescued by cygb1 overexpression. Both severe knockdown and null mutation of cygb1, established by the CRISPR/Cas9 technique, resulted in far more severe defects at early stages. Thus, it is highly likely that the downregulation of cygb1 is responsible for many, if not all, of the phenotypes of the kzt mutation. These results reveal a requirement for globin family proteins in vertebrate embryos, particularly in the differentiation and subsequent development of NCCs.
  English, Scientific journal
  DOI：https://doi.org/10.1016/j.ydbio.2020.12.016
  DOI ID：10.1016/j.ydbio.2020.12.016, PubMed ID：33358912
• Involvement of an Oct4-related PouV gene, pou5f3/pou2, in neurogenesis in the early neural plate of zebrafish embryos.　　　　　　　　　　　　　　　
  Inomata C; Yuikawa T; Nakayama-Sadakiyo Y; Kobayashi K; Ikeda M; Chiba M; Konishi C; Ishioka A; Tsuda S; Yamasu K
  Developmental Biology, Volume：457, Number：1, First page：30, Last page：42, Jan. 2020, [Reviewed]
• Horizontal Boundary Cells, a Special Group of Somitic Cells, Play Crucial Roles in the Formation of Dorsoventral Compartments in Teleost Somite　　　　　　　　　　　　　　　
  Kota Abe; Atsuko Shimada; Sayaka Tayama; Hotaka Nishikawa; Takuya Kaneko; Sachiko Tsuda; Akari Karaiwa; Takaaki Matsui; Tohru Ishitani; Hiroyuki Takeda
  Cell Reports, Volume：27, Number：3, First page：928, Last page：939, Apr. 2019, [Reviewed]
  Abe et al. find horizontal boundary cells (HBCs) crucial players for the formation of the dorsoventral compartments of the teleost myotome. HBCs express Hhip, which is necessary for the refinement of the boundary, and they contribute to the horizontal myoseptum, an anatomical structure dividing the dorsoventral compartments.
  Scientific journal
  DOI：https://doi.org/10.1016/j.celrep.2019.03.068
  Scopus：https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85064182923&origin=inward
  Scopus Citedby：https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85064182923&origin=inward
  DOI ID：10.1016/j.celrep.2019.03.068, eISSN：2211-1247, PubMed ID：30995487, SCOPUS ID：85064182923
• 4D imaging identifies dynamic migration and the fate of gbx2-expressing cells in the brain primordium of zebrafish.　　　　　　　　　　　　　　　
  Tsuda S; Hiyoshi K; Miyazawa H; Kinno R; Yamasu K; Corresponding Author
  Volume：690, First page：112, Last page：119, Jan. 2019, [Reviewed], [Lead, Corresponding]
• β-Oxidation in ghrelin-producing cells is important for ghrelin acyl-modification　　　　　　　　　　　　　　　
  Chika Ikenoya; Shota Takemi; Arisa Kaminoda; Sayaka Aizawa; Shiomi Ojima; Zhi Gong; Rakhi Chacrabati; Daisuke Kondo; Reiko Wada; Toru Tanaka; Sachiko Tsuda; Takafumi Sakai; Ichiro Sakata
  Scientific Reports, Volume：8, Number：1, First page：9176, Dec. 2018, [Reviewed]
  Ghrelin is a unique fatty acid-modified peptide hormone produced in the stomach and has important roles in energy homeostasis and gastrointestinal motility. However, the medium-chain fatty acid source for ghrelin acyl-modification is not known. We found that a fat-free diet and the removal of intestinal microbiota did not decrease acyl-ghrelin production in the stomach or plasma acyl-ghrelin levels in mice. RT-PCR analysis showed that genes involving fatty acid synthesis, metabolism, and transport were expressed in pancreas-derived ghrelinoma (PG-1) cells. Treatment with an irreversible inhibitor of carnitine palmitoyltransferase-1 (CPT-1) strongly decreased acylated ghrelin levels but did not affect ghrelin or ghrelin o-acyl transferase (GOAT) mRNA levels in PG-1 cells. Our results suggest that the medium-chain fatty acid used for the acyl-modification of ghrelin is produced in ghrelin-producing cells themselves by β-oxidation of long-chain fatty acids provided from the circulation.
  Nature Publishing Group, English, Scientific journal
  DOI：https://doi.org/10.1038/s41598-018-27458-2
  DOI ID：10.1038/s41598-018-27458-2, ISSN：2045-2322, PubMed ID：29907775, SCOPUS ID：85048721944
• Optical measurement of neuronal activity in the developing cerebellum of zebrafish using voltage-sensitive dye imaging.　　　　　　　　　　　　　　　
  Okumura K; Kakinuma H; Amo R; Okamoto H; Yamasu K; Tsuda S
  Neuroreport, Volume：29, Number：16, First page：1349, Last page：1354, Nov. 2018, [Reviewed], [Last, Corresponding], ［International magazine］
  Voltage-sensitive dye (VSD) imaging enables fast, direct, and simultaneous detection of membrane potentials from a population of neurons forming neuronal circuits. This enables the detection of hyperpolarization together with depolarization, whose balance plays a pivotal role in the function of many brain regions. Among these is the cerebellum, which contains a significant number of inhibitory neurons. However, the mechanism underlying the functional development remains unclear. In this study, we used a model system ideal to study neurogenesis by applying VSD imaging to the cerebellum of zebrafish larvae to analyze the neuronal activity of the developing cerebellum, focusing on both excitation and inhibition. We performed in-vivo high-speed imaging of the entire cerebellum of the zebrafish, which was stained using Di-4-ANEPPS, a widely used VSD. To examine whether neuronal activity in the zebrafish cerebellum could be detected by this VSD, we applied electrical stimulation during VSD imaging, which showed that depolarization was detected widely in the cerebellum upon stimulation. These responses mostly disappeared following treatment with tetrodotoxin, indicating that Di-4-ANEPPS enabled optical measurement of neuronal activity in the developing cerebellum of zebrafish. Moreover, hyperpolarizing signals were also detected upon stimulation, but these were significantly reduced by treatment with picrotoxin, a GABAA receptor inhibitor, indicating that these responses represent inhibitory signals. This approach will enable a detailed analysis of the spatiotemporal dynamics of the excitation and inhibition in the cerebellum along its developmental stages, leading to a deeper understanding of the functional development of the cerebellum in vertebrates.
  English, Scientific journal
  DOI：https://doi.org/10.1097/WNR.0000000000001113
  DOI ID：10.1097/WNR.0000000000001113, ISSN：0959-4965, PubMed ID：30192301
• Optical interrogation of neuronal circuitry in zebrafish using genetically encoded voltage indicators　　　　　　　　　　　　　　　
  Hiroaki Miyazawa; Kanoko Okumura; Kanae Hiyoshi; Kazuhiro Maruyama; Hisaya Kakinuma; Ryunosuke Amo; Hitoshi Okamoto; Kyo Yamasu; Sachiko Tsuda
  Scientific Reports, Volume：8, Number：1, First page：6048, Last page：6048, Apr. 2018, [Reviewed], [Last, Corresponding], ［International magazine］
  Optical measurement of membrane potentials enables fast, direct and simultaneous detection of membrane potentials from a population of neurons, providing a desirable approach for functional analysis of neuronal circuits. Here, we applied recently developed genetically encoded voltage indicators, ASAP1 (Accelerated Sensor of Action Potentials 1) and QuasAr2 (Quality superior to Arch 2), to zebrafish, an ideal model system for studying neurogenesis. To achieve this, we established transgenic lines which express the voltage sensors, and showed that ASAP1 is expressed in zebrafish neurons. To examine whether neuronal activity could be detected by ASAP1, we performed whole-cerebellum imaging, showing that depolarization was detected widely in the cerebellum and optic tectum upon electrical stimulation. Spontaneous activity in the spinal cord was also detected by ASAP1 imaging at single-cell resolution as well as at the neuronal population level. These responses mostly disappeared following treatment with tetrodotoxin, indicating that ASAP1 enabled optical measurement of neuronal activity in the zebrafish brain. Combining this method with other approaches, such as optogenetics and behavioural analysis may facilitate a deeper understanding of the functional organization of brain circuitry and its development.
  English, Scientific journal
  DOI：https://doi.org/10.1038/s41598-018-23906-1
  DOI ID：10.1038/s41598-018-23906-1, PubMed ID：29662090, PubMed Central ID：PMC5902623
• Study of termination of postprandial gastric contractions in humans, dogs and Suncus murinus: role of motilin- and ghrelin-induced strong contraction　　　　　　　　　　　　　　　
  T. Mikami; K. Ito; H. O. Diaz-Tartera; P. M. Hellström; E. Mochiki; S. Takemi; T. Tanaka; S. Tsuda; T. Jogahara; I. Sakata; T. Sakai
  Acta Physiologica, Volume：222, Number：2, Feb. 2018, [Reviewed]
  Aim: Stomach contractions show two types of specific patterns in many species, that is migrating motor contraction (MMC) and postprandial contractions (PPCs), in the fasting and fed states respectively. We found gastric PPCs terminated with migrating strong contractions in humans, dogs and suncus. In this study, we reveal the detailed characteristics and physiological implications of these strong contractions of PPC. Methods: Human, suncus and canine gastric contractions were recorded with a motility-monitoring ingestible capsule and a strain-gauge force transducer. The response of motilin and ghrelin and its receptor antagonist on the contractions were studied by using free-moving suncus. Results: Strong gastric contractions were observed at the end of a PPC in human, dog and suncus models, and we tentatively designated this contraction to be a postprandial giant contraction (PPGC). In the suncus, the PPGC showed the same property as those of a phase III contraction of MMC (PIII-MMC) in the duration, motility index and response to motilin or ghrelin antagonist administration. Ghrelin antagonist administration in the latter half of the PPC (LH-PPC) attenuated gastric contraction prolonged the duration of occurrence of PPGC, as found in PII-MMC. Conclusion: It is thought that the first half of the PPC changed to PII-MMC and then terminated with PIII-MMC, suggesting that PPC consists of a digestive phase (the first half of the PPC) and a discharge phase (LH-PPC) and that LH-PPC is coincident with MMC. In this study, we propose a new approach for the understanding of postprandial contractions.
  Blackwell Publishing Ltd, English, Scientific journal
  DOI：https://doi.org/10.1111/apha.12933
  DOI ID：10.1111/apha.12933, ISSN：1748-1716, PubMed ID：28786555, SCOPUS ID：85029411372
• The role of gastrulation brain homeobox 2 (gbx2) in the development of the ventral telencephalon in zebrafish embryos
  Zhe Wang; Yukiko Nakayama; Sachiko Tsuda; Kyo Yamasu
  Differentiation, Volume：99, First page：28, Last page：40, Jan. 2018, [Reviewed]
  During vertebrate brain development, the gastrulation brain homeobox 2 gene (gbx2) is expressed in the forebrain, but its precise roles are still unknown. In this study, we addressed this issue in zebrafish (Danio rerio) first by carefully examining gbx2 expression in the developing forebrain. We showed that gbx2 was expressed in the telencephalon during late somitogenesis, from 18 h post-fertilization (hpf) to 24 hpf, and in the thalamic primordium after 26 hpf. In contrast, another gbx gene, gbx1, was expressed in the anterior-most ventral telencephalon after 36 hpf. Thus, the expression patterns of these two gbx genes did not overlap, arguing against their redundant function in the forebrain. Two-color fluorescence in situ hybridization (FISH) showed close relationships between the telencephalic expression of gbx2 and other forebrain-forming genes, suggesting that their interactions contribute to the regionalization of the telencephalon. FISH further revealed that gbx2 is expressed in the ventricular region of the telencephalon. By using transgenic fish in which gbx2 can be induced by heat shock, we found that gbx2 induction at 16 hpf repressed the expression of emx3, dlx2a, and six3b in the ventral telencephalon. Among secreted factor genes, bmp2b and wnt1 were repressed in the vicinity of the gbx2 domain in the telencephalon. The expression of forebrain-forming genes was examined in mutant embryos lacking gbx2, showing emx3 and dlx2a to be upregulated in the subpallium at 24 hpf. Taken together, these findings indicate that gbx2 contributes to the development of the subpallium through its repressive activities against other telencephalon-forming genes. We further showed that inhibiting FGF signaling and activating Wnt signaling repressed gbx2 and affected the regionalization of the telencephalon, supporting a functional link between gbx2, intracellular signaling, and telencephalon development.
  Elsevier Ltd, English, Scientific journal
  DOI：https://doi.org/10.1016/j.diff.2017.12.005
  DOI ID：10.1016/j.diff.2017.12.005, ISSN：1432-0436, SCOPUS ID：85039744685
• Comprehensive analysis of target genes in zebrafish embryos reveals gbx2 involvement in neurogenesis　　　　　　　　　　　　　　　
  Yukiko Nakayama; Chihiro Inomata; Tatsuya Yuikawa; Sachiko Tsuda; Kyo Yamasu
  DEVELOPMENTAL BIOLOGY, Volume：430, Number：1, First page：237, Last page：248, Oct. 2017, [Reviewed]
  It is well established that the gbx2 homeobox gene contributes to the positioning of the midbrain-hindbrain boundary (MHB) governing the development of adjacent brain regions in vertebrate embryos, but the specific aspects of the gene regulatory network regulated by gbx2 during brain development remain unclear. In the present study, we sought to comprehensively identify gbx2 target genes in zebrafish embryos by microarray analysis around the end of gastrulation, when the MHB is established, using transgenic embryos harboring heat-inducible gbx2. This analysis revealed that a large number of genes were either upregulated or downregulated following gbx2 induction, and the time course of induction differed depending on the genes. The differences in response to gbx2 were found by functional annotation analysis to be related to the functions and structures of the target genes. Among the significantly downregulated genes was her5, whose expression in the midbrain was precisely complementary to gbx2 expression around the MHB, suggesting that gbx2 expression in the anterior hindbrain restricts her5 expression to the midbrain. Because her5 represses neurogenesis, gbx2 may positively regulate neural development in its expression domain. Indeed, we showed further that gbx2 induction upregulated neural marker expression in the midbrain. Quantitative PCR analysis revealed that gbx2 upregulated the expression of the zebrafish proneural gene ebf2, whereas it repressed notchl a, which generally represses neurogenesis. Taken together, these results demonstrate that gbx2 not only functions to position the MHB but also regulates neurogenesis in the anterior hindbrain.
  ACADEMIC PRESS INC ELSEVIER SCIENCE, English, Scientific journal
  DOI：https://doi.org/10.1016/j.ydbio.2017.07.015
  DOI ID：10.1016/j.ydbio.2017.07.015, ISSN：0012-1606, eISSN：1095-564X, PubMed ID：28756106, Web of Science ID：WOS:000411302100021
• Underlying mechanism of the cyclic migrating motor complex in Suncus murinus: a change in gastrointestinal pH is the key regulator　　　　　　　　　　　　　　　
  Anupom Mondal; Kouhei Koyama; Takashi Mikami; Taichi Horita; Shota Takemi; Sachiko Tsuda; Ichiro Sakata; Takafumi Sakai
  Physiological Reports, Volume：5, Number：1, Jan. 2017, [Reviewed]
  In the fasted gastrointestinal (GI) tract, a characteristic cyclical rhythmic migrating motor complex (MMC) occurs in an ultradian rhythm, at 90–120�min time intervals, in many species. However, the underlying mechanism directing this ultradian rhythmic MMC pattern is yet to be completely elucidated. Therefore, this study aimed to identify the possible causes or factors that involve in the occurrence of the fasting gastric contractions by using Suncus murinus a small model animal featuring almost the same rhythmic MMC as that found in humans and dogs. We observed that either intraduodenal infusion of saline at pH 8 evoked the strong gastric contraction or continuously lowering duodenal pH to 3-evoked gastric phase II-like and phase III-like contractions, and both strong contractions were essentially abolished by the intravenous administration of MA 2029 (motilin receptor antagonist) and D-Lys3-GHRP6 (ghrelin receptor antagonist) in a vagus-independent manner. Moreover, we observed that the prostaglandin E2-alpha (PGE2-α) and serotonin type 4 (5HT4) receptors play important roles as intermediate molecules in changes in GI pH and motilin release. These results suggest a clear insight mechanism that change in the duodenal pH to alkaline condition is an essential factor for stimulating the endogenous release of motilin and governs the fasting MMC in a vagus-independent manner. Finally, we believe that the changes in duodenal pH triggered by flowing gastric acid and the release of duodenal bicarbonate through the involvement of PGE2-α and 5HT4 receptor are the key events in the occurrence of the MMC.
  American Physiological Society, English, Scientific journal
  DOI：https://doi.org/10.14814/phy2.13105
  DOI ID：10.14814/phy2.13105, ISSN：2051-817X, PubMed ID：28082431, SCOPUS ID：85009230741
• Optogenetic Mapping of Cerebellar Inhibitory Circuitry Reveals Spatially Biased Coordination of Interneurons via Electrical Synapses　　　　　　　　　　　　　　　
  Jinsook Kim; Soojung Lee; Sachiko Tsuda; Xuying Zhang; Brent Asrican; Bernd Gloss; Guoping Feng; George J. Augustine
  CELL REPORTS, Volume：7, Number：5, First page：1601, Last page：1613, Jun. 2014, [Reviewed]
  We used high-speed optogenetic mapping technology to examine the spatial organization of local inhibitory circuits formed by cerebellar interneurons. Transgenic mice expressing channelrhodopsin-2 exclusively in molecular layer interneurons allowed us to focally photostimulate these neurons, while measuring resulting responses in postsynaptic Purkinje cells. This approach revealed that interneurons converge upon Purkinje cells over a broad area and that at least seven interneurons form functional synapses with a single Purkinje cell. The number of converging interneurons was reduced by treatment with gap junction blockers, revealing that electrical synapses between interneurons contribute substantially to the spatial convergence. Remarkably, gap junction blockers affected convergence in sagittal slices, but not in coronal slices, indicating a sagittal bias in electrical coupling between interneurons. We conclude that electrical synapse networks spatially coordinate interneurons in the cerebellum and may also serve this function in other brain regions.
  CELL PRESS, English, Scientific journal
  DOI：https://doi.org/10.1016/j.celrep.2014.04.047
  DOI ID：10.1016/j.celrep.2014.04.047, ISSN：2211-1247, PubMed ID：24857665, Web of Science ID：WOS:000338324200025
• Next-generation transgenic mice for optogenetic analysis of neural circuits analysis of neural circuits　　　　　　　　　　　　　　　
  Brent Asrican; George J. Augustine; Ken Berglund; Susu Chen; Nick Chow; Karl Deisseroth; Guoping Feng; Bernd Gloss; Riichiro Hira; Carolin Hoffmann; Haruo Kasai; Malvika Katarya; Jinsook Kim; John Kudolo; Li Ming Lee; Shun Qiang Lo; James Mancuso; Masanori Matsuzaki; Ryuichi Nakajima; Li Qiu; Gregory Tan; Yanxia Tang; Jonathan T. Ting; Sachiko Tsuda; Lei Wen; Xuying Zhang; Shengli Zhao
  FRONTIERS IN NEURAL CIRCUITS, Volume：7, First page：160, Nov. 2013, [Reviewed]
  Here we characterize several new lines of transgenic mice useful for optogenetic analysis of brain circuit function. These mice express optogenetic probes, such as enhanced halorhodopsin or several different versions of channelrhodopsins, behind various neuron-specific promoters. These mice permit photoinhibition or photostimulation both in vitro and in vivo. Our results also reveal the important influence of fluorescent tags on optogenetic probe expression and function in transgenic mice.
  FRONTIERS MEDIA SA, English, Scientific journal
  DOI：https://doi.org/10.3389/fncir.2013.00160
  DOI ID：10.3389/fncir.2013.00160, ISSN：1662-5110, PubMed ID：24324405, Web of Science ID：WOS:000328276300001
• High-speed optogenetic circuit mapping　　　　　　　　　　　　　　　
  George J. Augustine; Susu Chen; Harin Gill; Malvika Katarya; Jinsook Kim; John Kudolo; Li Ming Lee; Hyunjeong Lee; Shun Qiang Lo; Ryuichi Nakajima; Min-Yoon Park; Gregory Tan; Yanxia Tang; Peggy Teo; Sachiko Tsuda; Lei Wen; Su-In Yoon
  OPTOGENETICS: OPTICAL METHODS FOR CELLULAR CONTROL, Volume：8586, First page：858603, 2013, [Reviewed]
  Scanning small spots of laser light allows mapping of synaptic circuits in brain slices from transgenic mice expressing channelrhodopsin-2 (ChR2). The laser spots photostimulate presynaptic neurons expressing ChR2, while postsynaptic responses can be monitored in neurons that do not express ChR2. Correlating the location of the light spot with the amplitude of the postsynaptic response elicited at that location yields maps of the spatial organization of the synaptic circuits. This approach yields maps within minutes, which is several orders of magnitude faster than can be achieved with conventional paired electrophysiological methods. We have applied this high-speed technique to map local circuits in many brain regions. In cerebral cortex, we observed that maps of excitatory inputs to pyramidal cells were qualitatively different from those measured for interneurons within the same layers of the cortex. In cerebellum, we have used this approach to quantify the convergence of molecular layer interneurons on to Purkinje cells. The number of converging interneurons is reduced by treatment with gap junction blockers, indicating that electrical synapses between interneurons contribute substantially to the spatial convergence. Remarkably, gap junction blockers affect convergence in sagittal cerebellar slices but not in coronal slices, indicating sagittal polarization of electrical coupling between interneurons. By measuring limb movement or other forms of behavioral output, this approach also can be used in vivo to map brain circuits non-invasively. In summary, ChR2-mediated high-speed mapping promises to revolutionize our understanding of brain circuitry.
  SPIE-INT SOC OPTICAL ENGINEERING, English, International conference proceedings
  DOI：https://doi.org/10.1117/12.2012404
  DOI ID：10.1117/12.2012404, ISSN：0277-786X, Web of Science ID：WOS:000322901400002
• Probing the function of neuronal populations: Combining micromirror-based optogenetic photostimulation with voltage-sensitive dye imaging　　　　　　　　　　　　　　　
  Sachiko Tsuda; Michelle Z. L. Kee; Catarina Cunha; Jinsook Kim; Ping Yan; Leslie M. Loew; George J. Augustine
  NEUROSCIENCE RESEARCH, Volume：75, Number：1, First page：76, Last page：81, Jan. 2013, [Reviewed], [Lead]
  Recent advances in our understanding of brain function have come from using light to either control or image neuronal activity. Here we describe an approach that combines both techniques: a micromirror array is used to photostimulate populations of presynaptic neurons expressing channelrhodopsin-2, while a red-shifted voltage-sensitive dye allows optical detection of resulting postsynaptic activity. Such technology allowed us to control the activity of cerebellar interneurons while simultaneously recording inhibitory responses in multiple Purkinje neurons, their postsynaptic targets. This approach should substantially accelerate our understanding of information processing by populations of neurons within brain circuits. (C) 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
  ELSEVIER IRELAND LTD, English, Scientific journal
  DOI：https://doi.org/10.1016/j.neures.2012.11.006
  DOI ID：10.1016/j.neures.2012.11.006, ISSN：0168-0102, eISSN：1872-8111, PubMed ID：23254260, Web of Science ID：WOS:000316435700013
• Optogenetic mapping of brain circuitry　　　　　　　　　　　　　　　
  George J. Augustine, Ken Berglund, Harin Gill, Carolin Hoffmann, Malvika Katarya, Jinsook Kim, John Kudolo, Li Ming Lee, Molly Lee, Daniel Lo, Ryuichi Nakajima, Min Yoon Park, Gregory Tan, Yanxia Tang, Peggy Teo, Sachiko Tsuda, Lei Wen, and Su-In Yoon,
  SPIE Nanosystems in Engineering and Medicine, Volume：8548, First page：85483Y, 2012, [Reviewed]
• Optogenetic probing of functional brain circuitry　　　　　　　　　　　　　　　
  James J. Mancuso; Jinsook Kim; Soojung Lee; Sachiko Tsuda; Nicholas B. H. Chow; George J. Augustine
  EXPERIMENTAL PHYSIOLOGY, Volume：96, Number：1, First page：26, Last page：33, Jan. 2011, [Reviewed]
  Recently developed optogenetic technologies offer the promise of high-speed mapping of brain circuitry. Genetically targeted light-gated channels and pumps, such as channelrhodopsins and halorhodopsin, allow optical control of neuronal activity with high spatial and temporal resolution. Optogenetic probes of neuronal activity, such as Clomeleon and Mermaid, allow light to be used to monitor the activity of a genetically defined population of neurons. Combining these two complementary sets of optogenetic probes will make it possible to perform all-optical circuit mapping. Owing to the improved efficiency and higher speed of data acquisition, this hybrid approach should enable high-throughput mapping of brain circuitry.
  WILEY-BLACKWELL PUBLISHING, INC, English
  DOI：https://doi.org/10.1113/expphysiol.2010.055731
  DOI ID：10.1113/expphysiol.2010.055731, ISSN：0958-0670, PubMed ID：21056968, Web of Science ID：WOS:000285356800005
• FAK-mediated extracellular signals are essential for interkinetic nuclear migration and planar divisions in the neuroepithelium　　　　　　　　　　　　　　　
  Sachiko Tsuda; Tadao Kitagawa; Shigeo Takashima; Shuichi Asakawa; Nobuyoshi Shimizu; Hiroshi Mitani; Akihiro Shima; Makiko Tsutsumi; Hiroshi Hori; Kiyoshi Naruse; Yuji Ishikawa; Hiroyuki Takeda
  JOURNAL OF CELL SCIENCE, Volume：123, Number：3, First page：484, Last page：496, Feb. 2010, [Reviewed], [Lead]
  During the development of the vertebrate nervous system, mitosis of neural progenitor cells takes place near the lumen, the apical side of the neural tube, through a characteristic movement of nuclei known as interkinetic nuclear migration (INM). Furthermore, during the proliferative period, neural progenitor cells exhibit planar cell divisions to produce equivalent daughter cells. Here, we examine the potential role of extracellular signals in INM and planar divisions using the medaka mutant tacobo (tab). This tab mutant shows pleiotropic phenotypes, including neurogenesis, and positional cloning identified tab as laminin gamma 1 (lamc1), providing a unique framework to study the role of extracelluar signals in neurogenesis. In tab mutant neural tubes, a number of nuclei exhibit abnormal patterns of migration leading to basally mislocalized mitosis. Furthermore, the orientation of cell division near the apical surface is randomized. Probably because of these defects, neurogenesis is accelerated in the tab neural tube. Detailed analyses demonstrate that extracellular signals mediated by the FAK pathway regulate INM and planar divisions in the neuroepithelium, possibly through interaction with the intracellular dynein-motor system.
  COMPANY OF BIOLOGISTS LTD, English, Scientific journal
  DOI：https://doi.org/10.1242/jcs.057851
  DOI ID：10.1242/jcs.057851, ISSN：0021-9533, eISSN：1477-9137, PubMed ID：20067997, Web of Science ID：WOS:000274337800019
• Phenotypic analysis of a novel chordin mutant in medaka　　　　　　　　　　　　　　　
  Shigeo Takashima; Atsuko Shimada; Daisuke Kobayashi; Hayato Yokoi; Takanori Narita; Tomoko Jindo; Takahiro Kage; Tadao Kitagawa; Tetsuaki Kimura; Koshin Sekimizu; Akimitsu Miyake; Davin H. E. Setiamarga; Ryohei Murakami; Sachiko Tsuda; Shinya Ooki; Ken Kakihara; Motoki Hojo; Kiyoshi Naruse; Hiroshi Mitani; Akihiro Shima; Yuji Ishikawa; Kazuo Araki; Yumiko Saga; Hiroyuki Takeda
  DEVELOPMENTAL DYNAMICS, Volume：236, Number：8, First page：2298, Last page：2310, Aug. 2007, [Reviewed]
  We have isolated and characterized a ventralized mutant in medaka (the Japanese killifish; Oryzias latipes), which turned out to have a mutation in the chordin gene. The mutant exhibits ventralization of the body axis, malformation of axial bones, over-bifurcation of yolk sac blood vessels, and laterality defects in internal organs. The mutant exhibits variability of phenotypes, depending on the culture temperature, from embryos with a slightly ventralized phenotype to those without any head and trunk structures. Taking advantages of these variable and severe phenotypes, we analyzed the role of Chordin-dependent tissues such as the notochord and Kupffer's vesicle (KV) in the establishment of left-right axis in fish. The results demonstrate that, in the absence of the notochord and KV, the medaka lateral plate mesoderm autonomously and bilaterally expresses spaw gene in a default state.
  WILEY-LISS, English, Scientific journal
  DOI：https://doi.org/10.1002/dvdy.21245
  DOI ID：10.1002/dvdy.21245, ISSN：1058-8388, PubMed ID：17654721, Web of Science ID：WOS:000248838400025
• Right-elevated expression of charon is regulated by fluid flow in medaka Kupffer's vesicle　　　　　　　　　　　　　　　
  Motoki Hojo; Shigeo Takashima; Daisuke Kobayashi; Akira Sumeragi; Atsuko Shimada; Tatsuya Tsukahara; Hayato Yokoi; Takanori Narita; Tomoko Jindo; Takahiro Kage; Tadao Kitagawa; Tetsuaki Kimura; Koshin Sekimizu; Akimitsu Miyake; Davin Setiamarga; Ryohei Murakami; Sachiko Tsuda; Shinya Ooki; Ken Kakihara; Kiyoshi Naruse; Hiroyuki Takeda
  DEVELOPMENT GROWTH & DIFFERENTIATION, Volume：49, Number：5, First page：395, Last page：405, Jun. 2007, [Reviewed]
  Recent studies have revealed that a cilium-generated liquid flow in the node has a crucial role in the establishment of the left-right (LR) axis in the mouse. In fish, Kupffer's vesicle (KV), a teleost-specific spherical organ attached to the tail region, is known to have an equivalent role to the mouse node during LR axis formation. However, at present, there has been no report of an asymmetric gene expressed in KV under the control of fluid flow. Here we report the earliest asymmetric gene in teleost KV, medaka charon, and its regulation. Charon is a member of the Cerberus/DAN family of proteins, first identified in zebrafish. Although zebrafish charon was reported to be symmetrically expressed in KV, medaka charon displays asymmetric expression with more intense expression on the right side. This asymmetric expression was found to be regulated by KV flow because symmetric and up-regulated charon expression was observed in flow-defective embryos with immotile cilia or disrupted KV. Taken together, medaka charon is a reliable gene marker for LR asymmetry in KV and thus, will be useful for the analysis of the early steps downstream of the fluid flow.
  BLACKWELL PUBLISHING, English, Scientific journal
  DOI：https://doi.org/10.1111/j.1440-169x.2007.00937.x
  DOI ID：10.1111/j.1440-169x.2007.00937.x, ISSN：0012-1592, eISSN：1440-169X, PubMed ID：17547649, Web of Science ID：WOS:000247777800004

• Cellular and molecular mechanisms for the establishment of the lifelong dorsoventral compartment boundary in the teleost trunk　　　　　　　　　　　　　　　
  Kota Abe; Sayaka Tayama; Sachiko Tsuda; Atsuko Shimada; Hiroyuki Takeda
  MECHANISMS OF DEVELOPMENT, Volume：145, First page：S74, Last page：S74, Jul. 2017
  ELSEVIER SCIENCE BV, English, Summary international conference
  DOI：https://doi.org/10.1016/j.mod.2017.04.174
  DOI ID：10.1016/j.mod.2017.04.174, ISSN：0925-4773, eISSN：1872-6356, Web of Science ID：WOS:000402994800248

• In vivo optical detection of membrane potentials in the cerebellum: voltage imaging of zebrafish, In Measuring Cerebellar Function (Ed: Sillito S)　　　　　　　　　　　　　　　
  Hiyoshi K; Fukuda N; Shiraishi A; Tsuda S, [Contributor], 229-244
  Springer, Dec. 2021
• Optogenetics. In: Gerlai, R.T. (Ed.), Behavioral and Neural Genetics of Zebrafish.　　　　　　　　　　　　　　　
  Sachiko Tsuda, [Contributor], pp. 279–292
  Elsevier, Academic Press, Apr. 2020
• Optogenetics Enables Selective Control of Cellular Electrical Activity. “Molecular Neuroendocrinology: From Genome to Physiology”　　　　　　　　　　　　　　　
  Ryuichi Nakajima; Sachiko Tsuda; Jinsook Kim; George Augustine, [Joint work], 275–300
  Wiley-Blackwell, 2016

• 小型魚類を用いた集団行動の神経基盤の理解へ　　　　　　　　　　　　　　　
  津田佐知子
  Aug. 2024, [Invited]
• 魚類における集団行動「群れ」の神経基盤とその発達を探る　　　　　　　　　　　　　　　
  津田 佐知子
  Jul. 2024, [Invited]
  English, Nominated symposium
• 光で膜電位ダイナミクスを観る -小型魚類における光イメージング-　　　　　　　　　　　　　　　
  津田佐知子
  May 2024, [Invited]
  Nominated symposium
• プルキンエ細胞集団の時空間ダイナミクスに観る 小脳発達そして群れ形成　　　　　　　　　　　　　　　
  津田佐知子
  Mar. 2024, [Invited]
  Nominated symposium
• Spatiotemporal Dynamics of Purkinje Cell Populations and its Development　　　　　　　　　　　　　　　
  Sachiko Tsuda
  Gordon Research Conference Cerebellum, Aug. 2023, [Invited]
  Aug. 2023
• ゼブラフィッシュにおける群れ行動と小脳プルキンエ細胞の関係　　　　　　　　　　　　　　　
  大湯 翼; 齋藤 魁登; 宮成 和浩; 佐藤 大我; 藤井 慶輔; 津田 佐知子
  Aug. 2023
• Studying brain development with light　　　　　　　　　　　　　　　
  Sachiko Tsuda
  Dec. 2022, [Invited]
  Nominated symposium
• Optical recording of the membrane potential and brain development　　　　　　　　　　　　　　　
  津田佐知子
  埼玉大学先端産業国際ラボラトリー メディカルイノベーション研究ユニット 第22回ワークショップ バイオイメージングの最前線－生体分子の可視化ー, Dec. 2022, [Invited]
• How do neurons behave in populations and how are they formed during the development? -Spatiotemporal analysis in the zebrafish cerebellum-　　　　　　　　　　　　　　　
  Sachiko Tsuda
  IBRO-APRC Advanced School of Neuroscience 2022: Bioimaging and Proteogenomics for Cell-Based and Animal Research, Nov. 2022, [Invited]
  Public discourse
• 小型魚類の群れ行動における 小脳プルキンエ細胞の機能　　　　　　　　　　　　　　　
  齋藤魁登; 佐藤大我; 津田佐知子
  Sep. 2022
  Oral presentation
• Adaptation and Development of the Cerebellum in view of Eye Movements　　　　　　　　　　　　　　　
  Tomoya Murayama; Kanae Hiyoshi; Kaito Saito; Ryunosuke Togawa; Norihiro Katayama; Sachiko Tsuda
  Sep. 2022
  Poster presentation
• Voltage imaging for the study of brain function and development in zebrafish　　　　　　　　　　　　　　　
  Sachiko Tsuda
  Merocyanine 540 and FlaSh Celebration, Aug. 2022, [Invited]
  Invited oral presentation
• Population imaging of neurons in the zebrafish brain by genetically encoded voltage indicator, ArcLight　　　　　　　　　　　　　　　
  Asuka Shiraishi; Narumi Fukuda; Mari Hishinuma; Kanae Hiyoshi; Kyo Yamasu; Sachiko Tsuda
  Jul. 2022
  Poster presentation
• Optical probing of the resilience in olivocerebellar circuits by two-photon laser ablation and in vivo imaging of inferior olive neurons in zebrafish　　　　　　　　　　　　　　　
  Kanae Hiyoshi; Kaito Saito; Narumi Fukuda; Takahisa Matsuzaki; Hiroshi Yoshikawa; Sachiko Tsuda
  The 27th Japanese Medaka and Zebrafish Meeting, Sep. 2021
• Voltage imaging in zebrafish brain by Genetically encoded voltage indicator, ArcLight　　　　　　　　　　　　　　　
  Asuka Shiraishi; Narumi Fukuda; Mari Hishinuma; Kanae Hiyoshi; Kyo Yamasu; Sachiko Tsuda
  The 27th Japanese Medaka and Zebrafish Meeting, Sep. 2021
• In vivo application of genetically encoded voltage indicator ArcLight to the zebrafish brain　　　　　　　　　　　　　　　
  Asuka Shiraish; Narumi Fukuda; Mari Hishinuma; Kanae Hishinuma; Kanae Hiyoshi; Kyo Yamasu; Sachiko Tsuda
  Jul. 2021
• Clustered behavior of Purkinje cell populations and its changes in the developing cerebellum of zebrafish　　　　　　　　　　　　　　　
  Hiyoshi K; Okuda E; Fukuda N; Saito K; Yamasu K; Tsuda S
  Jul. 2021
  Oral presentation
• Optical interrogation of neural population dynamics in the zebrafish cerebellum　　　　　　　　　　　　　　　
  Sachiko Tsuda
  NIBB-Academia Sinica International Webinar of Aquatic Model Organisms for Basic Biology to Human Disease Models, Mar. 2021, [Invited]
  Invited oral presentation
• Clustered behavior of Purkinje cell populations in sensorimotor integration in the zebrafish cerebellum　　　　　　　　　　　　　　　
  Kanae Hiyoshi; Eri Okuda; Narumi Fukuda; Kaito Saito; Masahiko Hibi; Kyo Yamasu; Sachiko Tsuda
  The 26th Japanese Medaka and Zebrafish Meeting, Nov. 2020
  Oral presentation
• Anatomical and functional analysis of Inferior Olive-Cerebellar circuits in zebrafish larvae　　　　　　　　　　　　　　　
  Narumi Fukuda; Kanae Hiyoshi; Eri Okuda; Kyo Yamasu; Sachiko Tsuda
  The 26th Japanese Medaka and Zebrafish Meeting, Nov. 2020
  Oral presentation
• Neural population dynamics in the cerebellar circuits: Calcium and Voltage imaging in Zebrafish larvae　　　　　　　　　　　　　　　
  Sachiko Tsuda
  The 53th Annual Meeting of Japanese Society for Developmental Biologists, Mini Symposium "The Cerebellum: Evolution, Development and Neuronal Circuits", May 2020, [Invited]
  Public symposium
• Identifying functional compartments in the developing cerebellum: Calcium and voltage imaging in zebrafish　　　　　　　　　　　　　　　
  K. Hiyoshi; N. Fukuda; K. Okumura; K. Yamasu; S. Tsuda
  49th Annual Meeting of Society for Neuroscience, Oct. 2019, [International conference]
  English, Oral presentation
• 眼球運動におけるプルキンエ細胞の集団活動にみる小型魚類の小脳区画と発達 -魚を用いて小脳の構築メカニズムに迫る-　　　　　　　　　　　　　　　
  津田 佐知子
  Aug. 2019, [Invited], [Domestic conference]
  Japanese, Invited oral presentation
• 3D structure of functional compartments in the developing cerebellum: Spatiotemporal analysis in zebrafish　　　　　　　　　　　　　　　
  Kanae Hiyoshi; Narumi Fukuda; Kanoko Okumura; Kyo Yamasu; Sachiko Tsuda
  The 42th Annual Meeting of the Japan Neuroscience Society, Jul. 2019, [Domestic conference]
  English, Oral presentation
• Uncovering functional development of the cerebellum by voltage imaging in zebrafish　　　　　　　　　　　　　　　
  Tsuda Sachiko
  The 42th annual meeting of Japanese Neuroscience Society (Symposium: Voltage imaging: What's New? ), Jul. 2019, [Invited], [Domestic conference]
  Nominated symposium
• 小型魚類ゼブラフィッシュに観る小脳神経回路とその発達　　　　　　　　　　　　　　　
  津田 佐知子
  Jun. 2019, [Invited], [Domestic conference]
  Japanese, Invited oral presentation
• Spatiotemporal analysis of functional compartments in the developing cerebellum by calcium and voltage imaging　　　　　　　　　　　　　　　
  Sachiko Tsuda
  The 14th International Zebrafish Conference, Jun. 2019, [International conference]
  English, Oral presentation
• Probing the functional compartmentalization of the cerebellum in larval zebrafish　　　　　　　　　　　　　　　
  Sachiko Tsuda
  LB Cohen Symposium, May 2019, [Invited], [International conference]
  English, Invited oral presentation
• Unraveling 3D structure of functional compartments in the developing cerebellum: Spatiotemporal analysis in zebrafish　　　　　　　　　　　　　　　
  Kanae Hiyoshi; Narumi Fukuda; Kyo Yamasu; Sachiko Tsuda
  52nd Annual Meeting of the Japanese Society of Developmental Biologists, May 2019, [Domestic conference]
  English, Oral presentation
• Toward understanding functional development of the cerebellar circuitry with GFP and voltage imaging　　　　　　　　　　　　　　　
  Sachiko Tsuda
  5th Nagoya International Symposium on Neural Circuits: A Decade after "Discovery and Development of GFP": Expansion and Expectation, Mar. 2019, [Invited], [International conference]
• 小型魚類を用いた小脳機能モジュール形成の時空間的解析　　　　　　　　　　　　　　　
  津田 佐知子
  Dec. 2018, [Invited], [Domestic conference]
• Proving the functional development of the cerebellum: voltage imaging in the zebrafish brain　　　　　　　　　　　　　　　
  Tsuda Sachiko
  Institutional Seminar (School of Advanced Science and Engineering, Waseda University), Oct. 2018, [Invited]
  English, Public discourse
• Development of the functional circuitry in the cerebellum: voltage imaging in zebrafish　　　　　　　　　　　　　　　
  Tsuda Sachiko
  Voltage Imaging Mini Symposium at OIST, Oct. 2018, [Invited], [International conference]
  English, Invited oral presentation
• Voltage imaging of the developing brain using VSD and genetically-encoded voltage indicators in zebrafish　　　　　　　　　　　　　　　
  Tsuda Sachiko
  Merocyanine 540 45+1 Symposium, Sep. 2018, [Invited], [International conference]
  English, Invited oral presentation
• Optical measurement of neuronal activity in zebrafish using genetically encoded voltage indicators　　　　　　　　　　　　　　　
  Tsuda Sachiko
  The 24 the Japanese medaka and zebrafish meeting, Aug. 2018, [Domestic conference]
  English, Oral presentation
• Functional compartmentalization of the cerebellar circuits: three-dimensional analysis in zebrafish　　　　　　　　　　　　　　　
  Hyoshi K; Yamasu K; Tsuda S
  The 41st Annual Meeting of the Japan Neuroscience Society, Jul. 2018, [Domestic conference]
  English, Oral presentation
• Optical measurement of neuronal activity in zebrafish brain by genetically encoded voltage indicators　　　　　　　　　　　　　　　
  Kanoko Okumura; Hiroaki Miyazawa; Kanae Hiyoshi; Kazuhiro Maruyama; Hisashi Kakinuma; Ryunosuke Amo; Hitoshi Okamoto; Kyo Yamasu; Sachiko Tsuda
  Joint Annual Meeting of JSDB 51st and JSCB 70th, Jun. 2018, [Domestic conference]
  English, Oral presentation
• Optical interrogation of functional development of the cerebellar circuitry in zebrafish　　　　　　　　　　　　　　　
  Hiroaki Miyazawa; Kazuhiro Maruyama; Kanoko Okumura; Kanae Hiyoshi; Kyo Yamasu; Sachiko Tsuda
  The 88th Annual Meeting of the Zoological Society of Japan, Sep. 2017
• Optical interrogation of functional development of cerebellar circuitry in zebrafish　　　　　　　　　　　　　　　
  Tsuda Sachiko
  Life Engineering Symposium 2017 (The Society of Instruments and Control Engineers), Sep. 2017, [Invited]
• Optical interrogation of cerebellar circuitry via voltage sensor imaging in zebrafish　　　　　　　　　　　　　　　
  Hiroaki Miyazawa; Kazuhiro Maruyama; Kyo Yamasu; Sachiko Tsuda
  40th Annual Meeting of the Japan Neuroscience Society, Jul. 2017
• Functional organization of cerebellar circuitry and its development　　　　　　　　　　　　　　　
  Tsuda Sachiko
  Nov. 2016, [Invited]
• Dynamic migration of cell populations and functional compartmentalization in cerebellar development　　　　　　　　　　　　　　　
  Tsuda Sachiko
  MBI Seminar (Mechanobiology Institute, National University of Singapore), Oct. 2016, [Invited]
  English, Invited oral presentation
• Dynamic migration of cell populations and functional compartmentalization in cerebellar development: 4D imaging in zebrafish　　　　　　　　　　　　　　　
  Tsuda Sachiko
  7th Asia Oceania Zebrafish Meeting, Oct. 2016
• Structural and functional compartmentalization in cerebellar circuitry development: 4D imaging in zebrafish　　　　　　　　　　　　　　　
  Tsuda S; Kinno R; Miyazawa H; Yamasu K
  39th Annual Meeting of the Japan Neuroscience Society, Jul. 2016
• Probing the developmental process of functional circuitry in the cerebellum: an all-optogenetic approach in zebrafish　　　　　　　　　　　　　　　
  Tsuda S; Yamasu K
  38th Annual Meeting of the Japan Neuroscience Society, Jul. 2015
• Dynamic migratory behaviors of gbx2-expressing cells during brain compartmentalization -4D imaging in zebrafish embryos　　　　　　　　　　　　　　　
  Tsuda S; Yamasu K
  May 2015
• 神経組織形成のしくみと小脳神経回路の機能構成 -光技術を用いて構造と機能の関係に迫る-　　　　　　　　　　　　　　　
  Tsuda Sachiko
  Graduate School of Science, Nagoya University, May 2014, [Invited]
  Japanese, Invited oral presentation
• All optical circuit mapping: combining optogenetics and voltage sensitive dye imaging　　　　　　　　　　　　　　　
  Tsuda Sachiko
  Optical measurements of membrane potential symposium (Merocyanine 540 40 Symposium), Aug. 2012, [Invited], [International conference]
  English, Invited oral presentation
• Laminin regulates the interkinetic nuclear migration in neuroepithelial cells　　　　　　　　　　　　　　　
  Tsuda Sachiko; Hiroyuki Takeda
  The 41st Annual Meeting for the Japanese Society of Developmental Biologists, May 2008, [Domestic conference]
  English, Oral presentation

• JAPANESE SOCIETY OF DEVELOPMENTAL BIOLOGISTS
• THE JAPAN NEUROSCIENCE SOCIETY
• THE ZOOLOGICAL SOCIETY OF JAPAN
• THE MOLECULAR BIOLOGY SOCIETY OF JAPAN
• Society for Neuroscience

• 魚類の群れ行動を担う神経基盤および発達環境についての光解析　　　　　　　　　　　　　　　
  Apr. 2025 - Mar. 2029
  Principal investigator
• 光を用いた群れを担う神経ネットワークおよび発達環境の解明　　　　　　　　　　　　　　　
  Apr. 2024 - Mar. 2027
  Principal investigator
• 小型魚類を用いた群れナビゲーションの階層ダイナミクスについての光解析　　　　　　　　　　　　　　　
  01 Apr. 2024 - 31 Mar. 2026
  Grant amount(Total)：7540000, Direct funding：5800000, Indirect funding：1740000
  Grant number：24H01423
• 小型魚類に生体膜電位センサーを用いた水質バイオモニタリング技術の開発　　　　　　　　　　　　　　　
  Jul. 2023 - Mar. 2026
  Principal investigator
• Exploration and functional analysis of pregnant biomarkers related to mother-child mental health　　　　　　　　　　　　　　　
  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Apr. 2022 - Mar. 2026
  Saitama Medical University
  Grant amount(Total)：4160000, Direct funding：3200000, Indirect funding：960000
  Grant number：22K09625
• Investigation of the action of environmental factors on early embryos associated with autism spectrum disorder　　　　　　　　　　　　　　　
  Saitama Medical University, Grant for collaboration with Saitama University, Continued application 2024, Oct. 2024 - Sep. 2025
  Tomomi Sato; Sachiko Tsuda; Takeshi Kajihara; Tomohiro Kurisaki, School of Medicine, Saitama Medical University
  Grant number：23-J-03
• Studies on the pleiotropic functions and transcriptional regulation of gbx homeobox genes in the development of the vertebrate brain.　　　　　　　　　　　　　　　
  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), 01 Apr. 2021 - 31 Mar. 2025
  Saitama University, Coinvestigator
  Grant amount(Total)：4160000, Direct funding：3200000, Indirect funding：960000
  Grant number：21K06182
• Investigation to prevent maternal-fetal environmental factors affecting social behavior　　　　　　　　　　　　　　　
  Saitama Medical University, Oct. 2023 - Sep. 2024
  Tomomi Sato; Tsubasa Oyu; Sachiko Tsuda; Takeshi Kahjihara, School of Medicine, Saitama Medical University
  Grant number：23-J-03
• 小脳活動の光計測と操作による小型魚類の階層ナビゲーションの理解　　　　　　　　　　　　　　　
  16 Jun. 2022 - 31 Mar. 2024
  Grant amount(Total)：7800000, Direct funding：6000000, Indirect funding：1800000
  Grant number：22H05645
• ニューロンの集団ダイナミクスから見る小脳ネットワークの構築機構　　　　　　　　　　　　　　　
  2021 - 2023
  Principal investigator
• Functional analysis of neural circuits involving social communication behaviors using a fetal growth restriction model.　　　　　　　　　　　　　　　
  Saitama Medical University, Basic study, Oct. 2021 - Sep. 2022
  Sachiko Tsuda; Tomomi Sato; Kaito Saito, School of Medicine, Saitama Medical University
  Grant number：21-J-04
• 運動制御・学習の発達における小脳神経回路機能モジュールの時空間光解析　　　　　　　　　　　　　　　
  01 Apr. 2019 - 31 Mar. 2022
  Grant amount(Total)：4420000, Direct funding：3400000, Indirect funding：1020000
  Grant number：19K06756
• Regulatory mechanism of the differentiation of multipotent stem cells in the tailbud and spinal cord development in vertebrate embryos.　　　　　　　　　　　　　　　
  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), 01 Apr. 2018 - 31 Mar. 2022
  Yamasu Kyo, Saitama University, Coinvestigator
  Grant amount(Total)：4420000, Direct funding：3400000, Indirect funding：1020000
  In this study, we investigated the involvement of pou5f3, the homologue of mouse Oct4, in body axis elongation in the teleost fish, zebrafish (Danio rerio). First, we showed that pou5f3 is expressed at the posterior end of the elongating neural tube. In addition, functional inhibition/activation and mutant analyses suggested that pou5f3 actually promotes elongation of the neural tube and activates neurogenic genes. It was further shown that pou5f3 expression in the tail bud is regulated by various secreted signals. These data show that pou5f3 is expressed under the control of various signals in the posterior neural tube and promotes neural development of immature cells migrating from the tail bud.
  Grant number：18K06242
• 新規膜電位センサーによる個体レベルでの神経活動のリアルタイム光計測　　　　　　　　　　　　　　　
  2020 - 2022
  Principal investigator
• 小脳神経ネットワーク発達機構の解明を目指した 膜電位イメージングと統計解析技術の開発　　　　　　　　　　　　　　　
  2019 - 2022
  Principal investigator
• モデル動物等研究コーディネーティングネットワークによる希少・未診断疾患の病因遺伝子変異候補の機能解析研究　　　　　　　　　　　　　　　
  2018 - 2020
• 膜電位イメージングを用いた小型魚類の小脳発達機構　　　　　　　　　　　　　　　
  2018 - 2019
  Principal investigator
• The mechanism of compartmentalization of the cerebellar circuitry: an optogenetic approach using zebrafish　　　　　　　　　　　　　　　
  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B), Grant-in-Aid for Young Scientists (B), 01 Apr. 2015 - 31 Mar. 2017
  TSUDA Sachiko, Saitama University, Principal investigator
  Grant amount(Total)：4030000, Direct funding：3100000, Indirect funding：930000
  Although the general anatomical organization of the cerebellar neural circuitries is well defined, their functional development is still unresolved. To address this issue, especially focusing on cerebellar compartmentalization, we have applied optical approaches and behavior analysis to zebrafish. We conducted high-speed calcium imaging of neural activities of cerebellar Purkinje cells, which was combined with behavioral tests, such as optokinetic response (OKR) test and tactile stimulation. Specific populations of Purkinje cells were found to be activated during these tests, and their distribution patterns tend to differ along D-V axis. Furthermore, OKR was repressed by optogenetic stimulation targeting the activated regions. These findings suggest the structure and roles of the functional compartments in the developing cerebellum. We have also succeeded in detecting neuronal activities in zebrafish brain by using newly-developed voltage sensors, ASAP1.
  Grant number：15K20907
• 体性感覚受容における小脳区画 の神経基盤とその構築メカニズム　　　　　　　　　　　　　　　
  2016 - 2017
  Principal investigator
• Functional analysis of inhibitory circuitry in the cerebellum　　　　　　　　　　　　　　　
  Grass Foundation, Grass Fellowship, 2012 - 2012
  Sachiko Tsuda, Marine Biological Laboratory (USA), Principal investigator
• ラミニンγ1の神経管組織構築における役割-メダカを用いた発生遺伝学的解析-　　　　　　　　　　　　　　　
  2007 - 2008
  Grant amount(Total)：1800000, Direct funding：1800000
  Grant number：07J10806

• ゼブラフィッシュ個体の膜電位イメージング法　　　　　　　　　　　　　　　
  Patent right