Yamasaki Miwako
| Faculty of Medicine Physiological Science Anatomy | Associate Professor |
Last Updated :2025/06/07
■Researcher basic information
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Researcher number
- 10431305
J-Global ID
Educational Organization
- Bachelor's degree program, Departments of Medicine, School of Medicine
- Master's degree program, Graduate School of Medicine
- Doctoral (PhD) degree program, Graduate School of Medicine
■Career
Career
- Jun. 2016 - Present
Hokkaido University, Graduate School of Medicine, 准教授 - Apr. 2018 - Mar. 2019
Department of Cellular and Molecular Physiology, Yale University School of Medicine, Visiting Associate Professor - Mar. 2011 - May 2016
北海道大学 医学研究科, 講師 - Apr. 2007 - Feb. 2011
北海道大学 医学研究科, 助教 - Apr. 2006 - Mar. 2007
北海道大学 医学研究科, 助手 - Apr. 2003 - Mar. 2006
日本学術振興会 特別研究員(DC1) - Apr. 2002 - Mar. 2006
金沢大学大学院 医学系研究科 博士課程 - Apr. 1996 - Mar. 2002
Hokkaido University, School of Medicine
■Research activity information
Awards
- 2021, エクセレントティーチャー最優秀賞（講義、実習）
- Sep. 2019, 日本解剖学会 東北・北海道連合支部, 日本解剖学会 第65回東北・北海道連合支部学術集会 学会賞
- 2019, 北海道大学医学部, エクセレントティーチャー最優秀賞（講義、実習）
- Dec. 2014, 日本解剖学会, 平成２６年度 日本解剖学会奨励賞
入力経路・標的細胞依存的なグルタミン酸作動性シナプス制御機構の分子解剖学的基盤 - 2014, 北海道大学, 北海道大学教育総長賞（奨励賞）
- 2013, 北海道大学医学部, 最優秀教員特別賞（連続受賞）
- 2012, 北海道大学医学部, 最優秀教員賞
- 2011, 北海道大学医学部, 最優秀教員賞
Papers
- Preferential Localization of STIM1 to dendritic subsurface ER structures in Mouse Purkinje Cells.
Sakyo Nomura, Miwako Yamasaki, Taisuke Miyazaki, Kohtarou Konno, Masahiko Watanabe
The Journal of neuroscience : the official journal of the Society for Neuroscience, 14 Mar. 2025, [Peer-reviewed], [Lead author, Corresponding author], [International Magazine]
English, Scientific journal, The endoplasmic reticulum (ER) is the largest intracellular Ca2+ store, serving as the source and sink of intracellular Ca2+ The ER Ca2+ store is continuous yet organized into distinct subcompartments with spatial and functional heterogeneity. In cerebellar Purkinje cells (PCs), glutamatergic inputs trigger Ca2+ release from specific ER domains via inositol 1,4,5-trisphosphate receptors (IP3Rs) or ryanodine receptors (RyRs). Upon ER store depletion, refilling occurs through store-operated Ca2+ entry mediated by stromal interaction molecule-1 (STIM1). Although the significance of STIM1-mediated Ca2+ regulation within PCs is established, STIM1 localization in ER subcompartments in PCs for Ca2+ release and refilling remains elusive. Using validated antibodies, we demonstrated that STIM1 was predominantly localized as intense puncta along dendritic shafts in male and female mice, colocalizing with IP3R1 but not with RyR1. Immunoelectron microscopy revealed that STIM1 was accumulated in the subsurface ER in the dendritic shaft but excluded from those in the dendritic spine, the primary site of metabotropic glutamate receptor 1 (mGluR1)-IP3R-mediated Ca²⁺ signaling. Ca²⁺ imaging from control and STIM1-knockdown (STIM1-KD) PCs demonstrated that mGluR1-mediated Ca²⁺ release is more critically dependent on STIM1 than RyR-mediated Ca²⁺ release. These findings reveal a spatially organized ER network in PCs, where specialized ER subcompartments differentially regulate Ca²⁺ release and refilling. These findings suggest that STIM1 preferentially regulates Ca²⁺ dynamics associated with mGluR1-IP3R signaling, supporting specialized ER subcompartments for Ca²⁺ release and refilling. These findings highlight the intricate molecular-anatomical organization of dendritic ER Ca2+ signaling in PCs, which is crucial for synaptic plasticity and motor learning.Significance statement Intracellular calcium (Ca²⁺) signaling is essential for neuronal function, yet the organization of endoplasmic reticulum (ER) subcompartments that coordinate Ca²⁺ release and refilling remains unclear. This study demonstrates that stromal interaction molecule-1 (STIM1), a key regulator of store-operated Ca²⁺ entry, is predominantly localized to the subsurface ER in Purkinje cell dendrites, which had not been previously identified. STIM1 colocalizes with inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) and sarco/endoplasmic reticulum Ca²⁺-ATPase 2 (SERCA2) but is segregated from ryanodine receptor 1 (RyR1), highlighting specialized ER subdomains for Ca²⁺ release and refilling. These findings provide new insights into the molecular-anatomical organization of Ca²⁺ signaling in Purkinje cells, which plays key roles in synaptic plasticity, motor learning, and the pathophysiology of neurodegenerative diseases. - Molecular and Anatomical Strengthening of "Winner" Climbing Fiber Synapses in Developing Mouse Purkinje Cells.
Asako Nitta, Miwako Yamasaki, Taisuke Miyazaki, Kohtarou Konno, Haruto Yoshimura, Masahiko Watanabe
The Journal of neuroscience : the official journal of the Society for Neuroscience, 27 Feb. 2025, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, Neural circuits are refined by strengthening frequently used or advantaged synapses while eliminating redundant connections. In neonatal mice, cerebellar Purkinje cells (PCs) are initially innervated by multiple climbing fibers (CFs) of similar strength. By postnatal day 7 (P7), one CF, the "winner," is selectively strengthened and begins dendritic translocation by P9, while both "winner" and "loser" CFs temporarily maintain somatic synapses. Although the functional differentiation of CF inputs is well understood, their structural differentiation is less clear. In this study, we examined "winner" CF synapses in dendrites and both "winner" and "loser" synapses in the soma using serial electron microscopy and immunohistochemistry in C57BL/6 mice. We found that "winner" CF synapses, both in the soma and dendrites, developed more complex pre- and postsynaptic structures than "loser" CFs, with an expanded area of postsynaptic density. Additionally, "winner" CF synapses expressed significantly higher levels of AMPA-type glutamate receptors. Notably, only dendritic "winner" synapses showed increased levels of Rab3-interacting molecule RIM, a key presynaptic regulator of neurotransmitter release. These findings reveal the molecular and structural features that enable "winner" CFs to reinforce their synaptic strength and innervation, allowing them to outcompete other inputs during early development.Significance statement The neural circuit is refined by selectively strengthening specific synapses while eliminating redundant connections. In neonates, cerebellar Purkinje cell somata are innervated by multiple climbing fibers (CFs) with similar strength. Subsequently, a single CF is strengthened as the "winner," establishing a stable connection by translocating to dendrites. While the functional differentiation of CFs has been well-characterized, their structural differentiation remains largely unclear. Through serial electron microscopy and immunohistochemistry, we reveal that "winner" CF synapses elaborated synaptic structures with elevated AMPA receptor expression and presynaptic Rab-interacting molecule RIM. Thus, translocated "winner" CF synapses undergo molecular and anatomical strengthening, securing an irreversible competitive advantage over somatic CF synapses. The results provide a developmental basis for better understanding synaptic circuit refinement. - GFRα1 Promotes Axon Regeneration after Peripheral Nerve Injury by Functioning as a Ligand.
Tomoaki Suzuki, Ken Kadoya, Takeshi Endo, Miwako Yamasaki, Masahiko Watanabe, Norimasa Iwasaki
Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12, 4, e2400812, Jan. 2025, [Peer-reviewed], [International Magazine]
English, Scientific journal, The neurotrophic factor, Glial cell line derived neurotrophi factor (GDNF), exerts a variety of biological effects through binding to its receptors, GDNF family receptor alpha-1 (GFRα1), and RET. However, the existence of cells expressing GFRα1 but not RET raises the possibility that GFRα1 can function independently from RET. Here, it is shown that GFRα1 released from repair Schwann cells (RSCs) functions as a ligand in a GDNF-RET-independent manner to promote axon regeneration after peripheral nerve injury (PNI). Local administration of GFRα1 into injured nerve promoted axon regeneration, even more when combined with GDNF blockade. GFRα1 bound to a receptor complex consisting of NCAM and integrin α7β1 of dorsal root ganglion neurons in a GDNF-RET independent manner. This is further confirmed by the Ret Y1062F knock-in mice, which cannot transmit most of GDNF-RET signaling. Finally, local administration of GFRα1 into injured sciatic nerve promoted functional recovery. These findings reveal a novel role of GFRα1 as a ligand, the molecular mechanism supporting axon regeneration by RSCs, and a novel therapy for peripheral nerve repair. - Distinct release properties of glutamate/GABA co-transmission serve as a frequency-dependent filtering of supramammillary inputs.
Himawari Hirai, Kohtarou Konno, Miwako Yamasaki, Masahiko Watanabe, Takeshi Sakaba, Yuki Hashimotodani
eLife, 13, 16 Dec. 2024, [Peer-reviewed], [International Magazine]
English, Scientific journal, Glutamate and GABA co-transmitting neurons exist in several brain regions; however, the mechanism by which these two neurotransmitters are co-released from the same synaptic terminals remains unclear. Here, we show that the supramammillary nucleus (SuM) to dentate granule cell synapses, which co-release glutamate and GABA, exhibit differences between glutamate and GABA release properties in paired-pulse ratio, Ca2+-sensitivity, presynaptic receptor modulation, and Ca2+ channel-vesicle coupling configuration. Moreover, uniquantal synaptic responses show independent glutamatergic and GABAergic responses. Morphological analysis reveals that most SuM terminals form distinct glutamatergic and GABAergic synapses in proximity, each characterized by GluN1 and GABAAα1 labeling, respectively. Notably, glutamate/GABA co-transmission exhibits distinct short-term plasticities, with frequency-dependent depression of glutamate and frequency-independent stable depression of GABA. Our findings suggest that glutamate and GABA are co-released from different synaptic vesicles within the SuM terminals, and reveal that distinct transmission modes of glutamate/GABA co-release serve as frequency-dependent filters of SuM inputs. - MitoNEET reduces the mitochondrial oxidative phosphorylation during epithelial-mesenchymal transition
Haruka Handa, Yasuhito Onodera, Tsukasa Oikawa, Shingo Takada, Koji Ueda, Daiki Setoyama, Takashi Yokota, Miwako Yamasaki, Masahiko Watanabe, Yoshizuki Fumoto, Ari Hashimoto, Soichiro Hata, Masaaki Murakami, Hisataka Sabe
Cold Spring Harbor Laboratory, 29 Jul. 2024
Mitochondrial functions range from catabolic to anabolic, which are tightly coordinated to meet cellular demands for proliferation and motility. MitoNEET is a mitochondrial outer membrane protein with a CDGSH domain and is involved in mitochondrial function. Epithelial-to-mesenchymal transition (EMT) is the process in which cells lose their epithelial characteristics and acquire mesenchymal traits, such as motility, which is a vital step for organism development and wound-healing. Cellular motility is associated with high ATP consumption owing to lamellipodia formation, which is supported by upregulated oxidative phosphorylation (OXPHOS) capacity. However, how mitoNEET is involved in the regulation of OXPHOS capacity and subsequent cellular motility remains unclear. Here we show that loss of mitoNEET regulation during EMT impairs both OXPHOS enhancement and cell motility in non-transformed NMuMG mouse mammary gland epithelial cells. We found that mitoNEET is downregulated during EMT, and that the aberrant expression of mitoNEET abolishes the upregulation of OXPHOS, leading to the inhibition of cell motility. Furthermore, we found that mitoNEET topology may be crucial for the regulation of the mitochondrial electron transfer chain, suggesting an additional regulatory pathway for OXPHOS capacity. Our results demonstrate that mitochondrial OXPHOS capacity during EMT is partly regulated by the dynamics of the outer membrane protein. We believe that our findings are the first step towards understanding the mechanisms by which mitochondrial outer membrane protein topology affects organelle functions - Abundant extrasynaptic expression of α3β4-containing nicotinic acetylcholine receptors in the medial habenula-interpeduncular nucleus pathway in mice.
Asuka Tsuzuki, Miwako Yamasaki, Kohtarou Konno, Taisuke Miyazaki, Norio Takei, Susumu Tomita, Michisuke Yuzaki, Masahiko Watanabe
Scientific reports, 14, 1, 14193, 14193, 20 Jun. 2024, [Peer-reviewed], [Lead author, Corresponding author], [International Magazine]
English, Scientific journal, Nicotinic acetylcholine receptors (nAChRs) in the medial habenula (MHb)-interpeduncular nucleus (IPN) pathway play critical roles in nicotine-related behaviors. This pathway is particularly enriched in nAChR α3 and β4 subunits, both of which are genetically linked to nicotine dependence. However, the cellular and subcellular expression of endogenous α3β4-containing nAChRs remains largely unknown because specific antibodies and appropriate detection methods were unavailable. Here, we successfully uncovered the expression of endogenous nAChRs containing α3 and β4 subunits in the MHb-IPN pathway using novel specific antibodies and a fixative glyoxal that enables simultaneous detection of synaptic and extrasynaptic molecules. Immunofluorescence and immunoelectron microscopy revealed that both subunits were predominantly localized to the extrasynaptic cell surface of somatodendritic and axonal compartments of MHb neurons but not at their synaptic junctions. Immunolabeling for α3 and β4 subunits disappeared in α5β4-knockout brains, which we used as negative controls. The enriched and diffuse extrasynaptic expression along the MHb-IPN pathway suggests that α3β4-containing nAChRs may enhance the excitability of MHb neurons and neurotransmitter release from their presynaptic terminals in the IPN. The revealed distribution pattern provides a molecular and anatomical basis for understanding the functional role of α3β4-containing nAChRs in the crucial pathway of nicotine dependence. - Distinct roles of two thalamostriatal systems in learning processes of visual discrimination in common marmosets
Shigeki Kato, Masateru Sugawara, Miwako Yamasaki, Masahiko Watanabe, Ken-ichi Inoue, Katsuki Nakamura, Daisuke Koketsu, Satomi Chiken, Atsushi Nambu, Masahiko Takada, Kazuto Kobayashi
06 Jun. 2024 - Enhancement of Haloperidol-Induced Catalepsy by GPR143, an L-Dopa Receptor, in Striatal Cholinergic Interneurons.
Masami Arai, Etsuko Suzuki, Satoshi Kitamura, Momoyo Otaki, Kaori Kanai, Miwako Yamasaki, Masahiko Watanabe, Yuki Kambe, Koshi Murata, Yuuki Takada, Tetsu Arisawa, Kenta Kobayashi, Rei Tajika, Tomoyuki Miyazaki, Masahiro Yamaguchi, Michael Lazarus, Yu Hayashi, Shigeyoshi Itohara, Alban de Kerchove d'Exaerde, Hiroyuki Nawa, Ryang Kim, Haruhiko Bito, Toshihiko Momiyama, Daiki Masukawa, Yoshio Goshima
The Journal of neuroscience : the official journal of the Society for Neuroscience, 44, 11, 13 Mar. 2024, [International Magazine]
English, Scientific journal, Dopamine neurons play crucial roles in pleasure, reward, memory, learning, and fine motor skills and their dysfunction is associated with various neuropsychiatric diseases. Dopamine receptors are the main target of treatment for neurologic and psychiatric disorders. Antipsychotics that antagonize the dopamine D2 receptor (DRD2) are used to alleviate the symptoms of these disorders but may also sometimes cause disabling side effects such as parkinsonism (catalepsy in rodents). Here we show that GPR143, a G-protein-coupled receptor for L-3,4-dihydroxyphenylalanine (L-DOPA), expressed in striatal cholinergic interneurons enhances the DRD2-mediated side effects of haloperidol, an antipsychotic agent. Haloperidol-induced catalepsy was attenuated in male Gpr143 gene-deficient (Gpr143-/y ) mice compared with wild-type (Wt) mice. Reducing the endogenous release of L-DOPA and preventing interactions between GPR143 and DRD2 suppressed the haloperidol-induced catalepsy in Wt mice but not Gpr143-/y mice. The phenotypic defect in Gpr143-/y mice was mimicked in cholinergic interneuron-specific Gpr143-/y (Chat-cre;Gpr143flox/y ) mice. Administration of haloperidol increased the phosphorylation of ribosomal protein S6 at Ser240/244 in the dorsolateral striatum of Wt mice but not Chat-cre;Gpr143flox/y mice. In Chinese hamster ovary cells stably expressing DRD2, co-expression of GPR143 increased cell surface expression level of DRD2, and L-DOPA application further enhanced the DRD2 surface expression. Shorter pauses in cholinergic interneuron firing activity were observed after intrastriatal stimulation in striatal slice preparations from Chat-cre;Gpr143flox/y mice compared with those from Wt mice. Together, these findings provide evidence that GPR143 regulates DRD2 function in cholinergic interneurons and may be involved in parkinsonism induced by antipsychotic drugs. - All-synchronized picosecond pulses and time-gated detection improve the spatial resolution of two-photon STED microscopy in brain tissue imaging
Hirokazu Ishii, Kohei Otomo, Ching-Pu Chang, Miwako Yamasaki, Masahiko Watanabe, Hiroyuki Yokoyama, Tomomi Nemoto
PLOS ONE, 24 Aug. 2023, [Peer-reviewed]
Scientific journal - Glyoxal fixation: An approach to solve immunohistochemical problem in neuroscience research.
Kohtarou Konno, Miwako Yamasaki, Taisuke Miyazaki, Masahiko Watanabe
Science advances, 9, 28, eadf7084, 14 Jul. 2023, [Peer-reviewed], [International Magazine]
English, Scientific journal, The gold-standard fixative for immunohistochemistry is 4% formaldehyde; however, it limits antibody access to target molecules that are buried within specialized neuronal components, such as ionotropic receptors at the postsynapse and voltage-gated ion channels at the axon initial segment, often requiring additional antigen-exposing techniques to detect their authentic signals. To solve this problem, we used glyoxal, a two-carbon atom di-aldehyde. We found that glyoxal fixation greatly improved antibody penetration and immunoreactivity, uncovering signals for buried molecules by conventional immunohistochemical procedures at light and electron microscopic levels. It also enhanced immunosignals of most other molecules, which are known to be detectable in formaldehyde-fixed sections. Furthermore, we unearthed several specific primary antibodies that were once judged to be unusable in formaldehyde-fixed tissues, allowing us to successfully localize so far controversial synaptic adhesion molecule Neuroligin 1. Thus, glyoxal is a highly effective fixative for immunostaining, and a side-by-side comparison of glyoxal and formaldehyde fixation is recommended for routine immunostaining in neuroscience research. - PTPδ is a presynaptic organizer for the formation and maintenance of climbing fiber to Purkinje cell synapses in the developing cerebellum
Yuto Okuno, Kazuto Sakoori, Kyoko Matsuyama, Miwako Yamasaki, Masahiko Watanabe, Kouichi Hashimoto, Takaki Watanabe, Masanobu Kano
Frontiers in Molecular Neuroscience, 16, Frontiers Media SA, 22 Jun. 2023
Scientific journal, Functionally mature neural circuits are shaped during postnatal development by eliminating redundant synapses formed during the perinatal period. In the cerebellum of neonatal rodents, each Purkinje cell (PC) receives synaptic inputs from multiple (more than 4) climbing fibers (CFs). During the first 3 postnatal weeks, synaptic inputs from a single CF become markedly larger and those from the other CFs are eliminated in each PC, leading to mono-innervation of each PC by a strong CF in adulthood. While molecules involved in the strengthening and elimination of CF synapses during postnatal development are being elucidated, much less is known about the molecular mechanisms underlying CF synapse formation during the early postnatal period. Here, we show experimental evidence that suggests that a synapse organizer, PTPδ, is required for early postnatal CF synapse formation and the subsequent establishment of CF to PC synaptic wiring. We showed that PTPδ was localized at CF-PC synapses from postnatal day 0 (P0) irrespective of the expression of Aldolase C (Aldoc), a major marker of PC that distinguishes the cerebellar compartments. We found that the extension of a single strong CF along PC dendrites (CF translocation) was impaired in global PTPδ knockout (KO) mice from P12 to P29-31 predominantly in PCs that did not express Aldoc [Aldoc (–) PCs]. We also demonstrated via morphological and electrophysiological analyses that the number of CFs innervating individual PCs in PTPδ KO mice were fewer than in wild-type (WT) mice from P3 to P13 with a significant decrease in the strength of CF synaptic inputs in cerebellar anterior lobules where most PCs are Aldoc (–). Furthermore, CF-specific PTPδ-knockdown (KD) caused a reduction in the number of CFs innervating PCs with decreased CF synaptic inputs at P10-13 in anterior lobules. We found a mild impairment of motor performance in adult PTPδ KO mice. These results indicate that PTPδ acts as a presynaptic organizer for CF-PC formation and is required for normal CF-PC synaptic transmission, CF translocation, and presumably CF synapse maintenance predominantly in Aldoc (–) PCs. Furthermore, this study suggests that the impaired CF-PC synapse formation and development by the lack of PTPδ causes mild impairment of motor performance. - Execution of new trajectories toward a stable goal without a functional hippocampus.
Adrian J Duszkiewicz, Janine I Rossato, Andrea Moreno, Tomonori Takeuchi, Miwako Yamasaki, Lisa Genzel, Patrick Spooner, Santiago Canals, Richard G M Morris
Hippocampus, 33, 6, 769, 786, Jun. 2023, [International Magazine]
English, Scientific journal, The hippocampus is a critical component of a mammalian spatial navigation system, with the firing sequences of hippocampal place cells during sleep or immobility constituting a "replay" of an animal's past trajectories. A novel spatial navigation task recently revealed that such "replay" sequences of place fields can also prospectively map onto imminent new paths to a goal that occupies a stable location during each session. It was hypothesized that such "prospective replay" sequences may play a causal role in goal-directed navigation. In the present study, we query this putative causal role in finding only minimal effects of muscimol-induced inactivation of the dorsal and intermediate hippocampus on the same spatial navigation task. The concentration of muscimol used demonstrably inhibited hippocampal cell firing in vivo and caused a severe deficit in a hippocampal-dependent "episodic-like" spatial memory task in a watermaze. These findings call into question whether "prospective replay" of an imminent and direct path is actually necessary for its execution in certain navigational tasks. - Single-scan volumetric imaging throughout thick tissue specimens by one-touch installable light-needle creating device
Ching-Pu Chang, Kohei Otomo, Yuichi Kozawa, Hirokazu Ishii, Miwako Yamasaki, Masahiko Watanabe, Shunichi Sato, Ryosuke Enoki, Tomomi Nemoto
Scientific Reports, 12, 1, Springer Science and Business Media LLC, Dec. 2022
Scientific journal, Abstract
Biological tissues and their networks frequently change dynamically across large volumes. Understanding network operations requires monitoring their activities in three dimensions (3D) with single-cell resolution. Several researchers have proposed various volumetric imaging technologies. However, most technologies require large-scale and complicated optical setups, as well as deep expertise for microscopic technologies, resulting in a high threshold for biologists. In this study, we propose an easy-to-use light-needle creating device for conventional two-photon microscopy systems. By only installing the device in one position for a filter cube that conventional fluorescent microscopes have, single scanning of the excitation laser light beam excited fluorophores throughout over 200 μm thickness specimens simultaneously. Furthermore, the developed microscopy system successfully demonstrated single-scan visualization of the 3D structure of transparent YFP-expressing brain slices. Finally, in acute mouse cortical slices with a thickness of approximately 250 μm, we detected calcium activities with 7.5 Hz temporal resolution in the neuronal population. - Behavioral characteristics of dopamine D5 receptor knockout mice
Hitomi Sasamori, Toshiaki Asakura, Chiaki Sugiura, Youcef Bouchekioua, Naoya Nishitani, Masaaki Sato, Takayuki Yoshida, Miwako Yamasaki, Akira Terao, Masahiko Watanabe, Yu Ohmura, Mitsuhiro Yoshioka
Scientific Reports, 12, 1, Springer Science and Business Media LLC, Dec. 2022
Scientific journal, Abstract
Major psychiatric disorders such as attention-deficit/hyperactivity disorder and schizophrenia are often accompanied by elevated impulsivity. However, anti-impulsive drug treatments are still limited. To explore a novel molecular target, we examined the role of dopamine D5 receptors in impulse control using mice that completely lack D5 receptors (D5KO mice). We also measured spontaneous activity and learning/memory ability because these deficits could confound the assessment of impulsivity. We found small but significant effects of D5 receptor knockout on home cage activity only at specific times of the day. In addition, an analysis using the q-learning model revealed that D5KO mice displayed lower behavioral adjustment after impulsive actions. However, our results also showed that baseline impulsive actions and the effects of an anti-impulsive drug in D5KO mice were comparable to those in wild-type littermates. Moreover, unlike previous studies that used other D5 receptor-deficient mouse lines, we did not observe reductions in locomotor activity, working memory deficits, or severe learning deficits in our line of D5KO mice. These findings demonstrate that D5 receptors are dispensable for impulse control. Our results also indicate that time series analysis and detailed analysis of the learning process are necessary to clarify the behavioral functions of D5 receptors. - Nna1, Essential for Purkinje Cell Survival, Is also Associated with Emotion and Memory. 2022 Oct 26;23(21):12961. doi: 10.3390/ijms232112961. PMID: 36361749.
Zhou L, Konno K, Yamazaki M, Abe M, Natsume R, Watanabe M, Takebayashi H, Sakimura K
Int J Mol Sci., 23(21), 12961, 1, 16, Oct. 2022, [Peer-reviewed]
English, Scientific journal - Cyclophilin D regulates NETosis and inflammation in myeloperoxidase-antineutrophil cytoplasmic antibody-associated vasculitis.
Takashi Kudo, Daigo Nakazawa, Kanako Watanabe-Kusunoki, Masatoshi Kanda, Satoka Shiratori-Aso, Nobuya Abe, Saori Nishio, Jun-Ichiro Koga, Sari Iwasaki, Takahiro Tsuji, Yuichiro Fukasawa, Miwako Yamasaki, Masahiko Watanabe, Sakiko Masuda, Utano Tomaru, Masaaki Murakami, Yasuaki Aratani, Akihiro Ishizu, Tatsuya Atsumi
Arthritis & rheumatology (Hoboken, N.J.), 75, 1, 71, 83, 29 Jul. 2022, [International Magazine]
English, Scientific journal, OBJECTIVE: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is pathologically characterized by focal fibrinoid necrosis where ANCA-mediated neutrophil extracellular trap (NET) formation and subsequent endothelial necrosis occurs. Cyclophilin D (CypD) plays an important role in mediating cell necrosis and inflammation via opening of mitochondrial permeability transition pores (mPTP). Here, we examined the role of CypD in AAV pathogenesis. METHODS: In vitro, the role and mechanism of CypD in ANCA-stimulated neutrophils were assessed by immunostaining and electron microscopy. A comprehensive RNA sequencing analysis was performed on ANCA-treated murine neutrophils. To investigate the role of CypD in vivo, an-anti-MPO IgG-transfer AAV model or spontaneous AAV model mice were induced in CypD knockout or wild-type mice. RESULTS: In vitro, pharmacological and genetic inhibition of CypD suppressed ANCA-induced NET formation via the suppression of reactive oxygen species/cytochrome c release from the mitochondria. The analysis of RNA sequencing in ANCA-treated murine neutrophils revealed the involvement of inflammatory responses, and CypD deficiency reduced ANCA-induced alterations in gene expression. Furthermore, the upstream regulator analysis revealed the relevance of intracellular calcium (CypD activator) and cyclosporin (CypD inhibitor) in ANCA stimulation, indicating that CypD-dependent mPTP opening is associated with ANCA-induced neutrophil activation and NETosis. In both AAV models, the genetic deletion of CypD ameliorated crescentic glomerulonephritis via the inhibition of CypD-dependent neutrophil and endothelial necrosis. CONCLUSIONS: CypD targeting is a novel and specific therapeutic strategy for AAV via the resolution of necrotizing vasculitis. - Pathogenic neuropsychiatric effect of stress-induced microglial interleukin 12/23 axis in systemic lupus erythematosus.
Nobuya Abe, Masato Tarumi, Yuichiro Fujieda, Nobuhiko Takahashi, Kohei Karino, Mona Uchida, Michihito Kono, Yuki Tanaka, Rie Hasebe, Masaru Kato, Olga Amengual, Yoshiyuki Arinuma, Kenji Oku, Wakiro Sato, Khin Khin Tha, Miwako Yamasaki, Masahiko Watanabe, Tatsuya Atsumi, Masaaki Murakami
Annals of the rheumatic diseases, 11 Jul. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, OBJECTIVES: The central nervous system disorder in systemic lupus erythematosus (SLE), called neuropsychiatric lupus (NPSLE), is one of the most severe phenotypes with various clinical symptoms, including mood disorder, psychosis and delirium as diffuse neuropsychological manifestations (dNPSLE). Although stress is one of the aggravating factors for neuropsychiatric symptoms, its role in the pathogenesis of dNPSLE remains to be elucidated. We aimed to investigate stress effects on the neuropsychiatric pathophysiology in SLE using lupus-prone mice and patients' data. METHODS: Sleep disturbance stress (SDS) for 2 weeks was placed on 6-8-week-old female MRL/lpr and control mice. Behavioural phenotyping, histopathological analyses and gene and protein expression analyses were performed to assess SDS-induced neuroimmunological alterations. We also evaluated cytokines of the cerebrospinal fluid and brain regional volumes in patients with dNPSLE and patients with non-dNPSLE. RESULTS: SDS-subjected MRL/lpr mice exhibited less anxiety-like behaviour, whereas stressed control mice showed increased anxiety. Furthermore, stress strongly activated the medial prefrontal cortex (mPFC) in SDS-subjected MRL/lpr. A transcriptome analysis of the PFC revealed the upregulation of microglial activation-related genes, including Il12b. We confirmed that stress-induced microglial activation and the upregulation of interleukin (IL) 12/23p40 proteins and increased dendritic spines in the mPFC of stressed MRL/lpr mice. IL-12/23p40 neutralisation and tyrosine kinase 2 inhibition mitigated the stress-induced neuropsychiatric phenotypes of MRL/lpr mice. We also found a higher level of cerebrospinal fluid IL-12/23p40 and more atrophy in the mPFC of patients with dNPSLE than those with non-dNPSLE. CONCLUSIONS: The microglial IL-12/23 axis in the mPFC might be associated with the pathogenesis and a promising therapeutic target for dNPSLE. - Histochemical characterization of the dorsal raphe-periaqueductal grey dopamine transporter neurons projecting to the extended amygdala.
Qin Zhao, Tetsufumi Ito, Chika Soko, Yoshie Hori, Takafumi Furuyama, Hiroyuki Hioki, Kohtarou Konno, Miwako Yamasaki, Masahiko Watanabe, Satoshi Ohtsuka, Munenori Ono, Nobuo Kato, Ryo Yamamoto
eNeuro, 13 May 2022, [International Magazine]
English, Scientific journal, The dorsal raphe (DR) nucleus contains many tyrosine hydroxylase (TH) positive neurons which are regarded as dopaminergic (DA) neurons. These DA neurons in the DR and periaqueductal grey (PAG) region (DADR-PAG neurons) are a subgroup of the A10 cluster, which is known to be heterogeneous. This DA population projects to the central nucleus of the amygdala (CeA) and the bed nucleus of the stria terminalis (BNST) and has been reported to modulate various affective behaviors. To characterize, the histochemical features of DADR-PAG neurons projecting to the CeA and BNST in mice, the current study combined retrograde labeling with fluoro-gold (FG) and histological techniques, focusing on TH, dopamine transporter (DAT), vasoactive intestinal peptide (VIP), and vesicular glutamate transporter 2 (VGlut2). To identify putative DA neurons, DAT-Cre::Ai14 mice were used. It was observed that DATDR-PAG neurons consisted of the following two subpopulations: TH+/VIP- and TH-/VIP+ neurons. The DAT+/TH-/VIP+ subpopulation would be non-DA non-canonical DAT neurons. Anterograde labeling of DATDR-PAG neurons with AAV in DAT-Cre mice revealed that the fibers exclusively innervated the lateral part of the CeA and the oval nucleus of the BNST. Retrograde labeling with FG injections into the CeA or BNST revealed that the two subpopulations similarly innervated these regions. Furthermore, using VGlut2-Cre::Ai14 mice, it was turned out that the TH-/VIP+ subpopulations innervating both CeA and BNST were VGlut2-positive neurons. These two subpopulations of DATDR-PAG neurons, TH+/VIP- and TH-/VIP+, might differentially interfere with the extended amygdala, thereby modulating affective behaviors.Significance StatementDopaminergic (DA) neurons in the dorsal raphe (DR) and periaqueductal grey (PAG) regions have projections to the extended amygdala and have been reported to modulate various affective behaviors. These DA neurons are a subgroup of the A10 cluster, which is known to be heterogeneous. However, it remains unknown how heterogeneous subpopulations innervate the extended amygdala. We used the DA transporter as a DA neuron marker and found that the DAT DR-PAG neurons are composed of at least two subpopulations, DAT+/tyrosine hydroxylase (TH)+/vasoactive intestinal peptide (VIP)- putative DA neurons and DAT+/TH-/VIP+ putative non-DA glutamatergic neurons, innervating the extended amygdala similarly. These results indicate that the two subpopulations might differently modulate the affective behaviors controlled by the extended amygdala. - L-DOPA-Induced Neurogenesis in the Hippocampus Is Mediated Through GPR143, a Distinct Mechanism of Dopamine.
Yuka Kasahara, Daiki Masukawa, Kenta Kobayashi, Miwako Yamasaki, Masahiko Watanabe, Yoshio Goshima
Stem cells (Dayton, Ohio), 40, 2, 215, 226, 16 Mar. 2022, [International Magazine]
English, Scientific journal, Neurogenesis occurs in the hippocampus throughout life and is implicated in various physiological brain functions such as memory encoding and mood regulation. L-3,4-dihydroxyphenylalanine (L-DOPA) has long been believed to be an inert precursor of dopamine. Here, we show that L-DOPA and its receptor, GPR143, the gene product of ocular albinism 1, regulate neurogenesis in the dentate gyrus (DG) in a dopamine-independent manner. L-DOPA at concentrations far lower than that of dopamine promoted proliferation of neural stem and progenitor cells in wild-type mice under the inhibition of its conversion to dopamine; this effect was abolished in GPR143 gene-deficient (Gpr143-/y) mice. Hippocampal neurogenesis decreased during development and adulthood, and exacerbated depression-like behavior was observed in adult Gpr143-/y mice. Replenishment of GPR143 in the DG attenuated the impaired neurogenesis and depression-like behavior. Our findings suggest that L-DOPA through GPR143 modulates hippocampal neurogenesis, thereby playing a role in mood regulation in the hippocampus. - Activation of extrasynaptic kainate receptors drives hilar mossy cell activity.
Czarina Ramos, Stefano Lutzu, Miwako Yamasaki, Yuchio Yanagawa, Kenji Sakimura, Susumu Tomita, Masahiko Watanabe, Pablo E Castillo
The Journal of neuroscience : the official journal of the Society for Neuroscience, 22 Feb. 2022, [International Magazine]
English, Scientific journal, Mossy cells (MCs) of the dentate gyrus (DG) are key components of an excitatory associative circuit established by reciprocal connections with dentate granule cells (GCs). MCs are implicated in place field encoding, pattern separation and novelty detection, as well as in brain disorders such as temporal lobe epilepsy and depression. Despite their functional relevance, little is known about the determinants that control MC activity. Here, we examined whether MCs express functional kainate receptors (KARs), a subtype of glutamate receptors involved in neuronal development, synaptic transmission, and epilepsy. Using mouse hippocampal slices, we found that bath application of submicromolar and micromolar concentrations of the KAR agonist kainic acid induced inward currents and robust MC firing. These effects were abolished in GluK2 KO mice, indicating the presence of functional GluK2-containing KARs in MCs. In contrast to CA3 pyramidal cells, which are structurally and functionally similar to MCs and express synaptic KARs at mossy fiber (MF) inputs (i.e., GC axons), we found no evidence for KAR-mediated transmission at MF-MC synapses, indicating that most KARs at MCs are extrasynaptic. Immunofluorescence and immunoelectron microscopy analyses confirmed the extrasynaptic localization of GluK2-containing KARs in MCs. Finally, blocking glutamate transporters, a manipulation that increases extracellular levels of endogenous glutamate, was sufficient to induce KAR-mediated inward currents in MCs, suggesting that MC-KARs can be activated by increases in ambient glutamate. Our findings provide the first direct evidence of functional extrasynaptic KARs at a critical excitatory neuron of the hippocampus.SIGNIFICANCE STATEMENTHilar mossy cells (MCs) are an understudied population of hippocampal neurons that form an excitatory loop with dentate granule cells. MCs have been implicated in pattern separation, spatial navigation, and epilepsy. Despite their importance in hippocampal function and disease, little is known about how MC activity is recruited. Here, we show for the first time that MCs express extrasynaptic kainate receptors (KARs), a subtype of glutamate receptors critically involved in neuronal function and epilepsy. While we found no evidence for synaptic KARs in MCs, KAR activation induced strong action potential firing of MCs, raising the possibility that extracellular KARs regulate MC excitability in vivo and may also promote dentate gyrus hyperexcitability and epileptogenesis. - SIPA1L1/SPAR1 interacts with the neurabin family of proteins and is involved in GPCR signaling.
Ken Matsuura, Shizuka Kobayashi, Kohtarou Konno, Miwako Yamasaki, Takahiro Horiuchi, Takao Senda, Tomoatsu Hayashi, Kiyotoshi Satoh, Fumiko Arima-Yoshida, Kei Iwasaki, Lumi Negishi, Naomi Yasui-Shimizu, Kazuyoshi Kohu, Shigenori Kawahara, Yutaka Kirino, Tsutomu Nakamura, Masahiko Watanabe, Tadashi Yamamoto, Toshiya Manabe, Tetsu Akiyama
The Journal of neuroscience : the official journal of the Society for Neuroscience, 42, 12, 2448, 2473, 04 Feb. 2022, [International Magazine]
English, Scientific journal, SIPA1L1 (also known as SPAR1) has been proposed to regulate synaptic functions that are important in maintaining normal neuronal activities, such as regulating spine growth and synaptic scaling, as a component of the PSD-95/NMDA-R-complex. However, its physiological role remains poorly understood. Here, we performed expression analyses using super-resolution microscopy in mouse brain and demonstrated that SIPA1L1 is mainly localized to general submembranous regions in neurons, but surprisingly, not to PSD. Our screening for physiological interactors of SIPA1L1 in mouse brain identified spinophilin and neurabin-1, regulators of GPCR signaling, but rejected PSD-95/NMDA-R-complex components. Furthermore, Sipa1l1 -/- mice showed normal spine size distribution and NMDA-R-dependent synaptic plasticity. Nevertheless, Sipa1l1 -/- mice showed aberrant responses to α2-adrenergic receptor (a spinophilin target) or adenosine A1 receptor (a neurabin-1 target) agonist stimulation, and striking behavioral anomalies, such as hyperactivity, enhanced anxiety, learning impairments, social interaction deficits, and enhanced epileptic seizure susceptibility. Male mice were used for all experiments. Our findings revealed unexpected properties of SIPA1L1, suggesting a possible association of SIPA1L1 deficiency with neuropsychiatric disorders related to dysregulated GPCR signaling, such as epilepsy, attention deficit hyperactivity disorder (ADHD), autism, or fragile X syndrome.SIGNIFICANCE STATEMENTSIPA1L1 is thought to regulate essential synaptic functions as a component of the PSD-95/NMDA-R-complex. In our screening for physiological SIPA1L1-interactors, we identified GPCR-signaling regulators. Moreover, SIPA1L1 KO mice showed striking behavioral anomalies, which may be relevant to GPCR signaling. Our findings revealed an unexpected role of SIPA1L1, which may open new avenues for research on neuropsychiatric disorders that involve dysregulated GPCR signaling. Another important aspect of this paper is that we showed effective methods for checking PSD association and identifying native protein interactors that are difficult to solubilize. These results may serve as a caution for future claims about interacting proteins and PSD proteins, which could eventually save time and resources for researchers and avoid confusion in the field. - mGluR1 signaling in cerebellar Purkinje cells: Subcellular organization and involvement in cerebellar function and disease
Miwako Yamasaki, Atsu Aiba, Masanobu Kano, Masahiko Watanabe
Neuropharmacology, 194, 108629, 108629, Elsevier {BV}, Aug. 2021, [Lead author, Corresponding author], [International Magazine]
English, Scientific journal, The cerebellum is essential for the control, coordination, and learning of movements, and for certain aspects of cognitive function. Purkinje cells are the sole output neurons in the cerebellar cortex and therefore play crucial roles in the diverse functions of the cerebellum. The type 1 metabotropic glutamate receptor (mGluR1) is prominently enriched in Purkinje cells and triggers downstream signaling pathways that are required for functional and structural plasticity, and for synaptic responses. To understand how mGluR1 contributes to cerebellar functions, it is important to consider not only the operational properties of this receptor, but also its spatial organization and the molecular interactions that enable its proper functioning. In this review, we highlight how mGluR1 and its related signaling molecules are organized into tightly coupled microdomains to fulfill physiological functions. We also describe emerging evidence that altered mGluR1 signaling in Purkinje cells underlies cerebellar dysfunction in ataxias of human patients and mouse models. - Compartmentalized Input-Output Organization of Lugaro Cells in the Cerebellar Cortex.
Taisuke Miyazaki, Miwako Yamasaki, Kenji F Tanaka, Masahiko Watanabe
Neuroscience, 462, 89, 105, 10 May 2021, [International Magazine]
English, Scientific journal, Purkinje cells (PCs) are principal cerebellar neurons, and several classes of interneurons modulate their activity. Lugaro cells (LCs) are one such inhibitory interneuron with distinctive cytology and location, but still most enigmatic among cerebellar neurons. Here we serendipitously produced a novel transgenic mouse line, where a half of Yellow Cameleon (YC)(+) cells in the cerebellar cortex were judged to be LCs, and YC(+) LCs were estimated to constitute one-third of the total LC populations. Neurochemically, two-thirds of YC(+) LCs were dually GABAergic/glycinergic, with the rest being GABAergic. Beneath the PC layer, they extended a sheet of somatodendritic meshwork interconnected with neighboring LCs by adherens junctions, and received various inputs from climbing fibers, mossy fibers, granule cell axons, recurrent PC axons, Golgi cell axons, LC axons, and serotonergic fibers. Intriguingly, somatodendritic elements of individual LCs preferentially extended within a given cerebellar compartment defined by aldolase C expression. In turn, YC(+) LCs projected a dense lattice of ascending and transverse axons to the molecular layer, and innervated molecular layer interneurons (basket and stellate cells) and Golgi cells, but not PCs. Of note, ascending axons profusely innervated individual targets within a cerebellar compartment, while transverse axons ran across several compartments and innervated targets sparsely. This unique circuit configuration highlights that LCs integrate various excitatory, inhibitory, and modulatory inputs coming to the belonging cerebellar compartment and that, as an interneuron-selective interneuron, LCs can effectively disinhibit cerebellar cortical activities in a compartment-dependent manner through inhibition of inhibitory interneurons selectively targeting PCs and granule cells. - Fluorescent In Situ Hybridization for Sensitive and Specific Labeling
Miwako Yamasaki, Masahiko Watanabe
Neuromethods, 169, 145, 160, Humana Press Inc., 2021
English, In book - Spike firing attenuation of serotonin neurons in learned helplessness rats is reversed by ketamine.
Kouichi Hashimoto, Yosuke Yamawaki, Kenji Yamaoka, Takayuki Yoshida, Kana Okada, Wanqin Tan, Miwako Yamasaki, Yoshiko Matsumoto-Makidono, Reika Kubo, Hisako Nakayama, Tsutomu Kataoka, Takashi Kanematsu, Masahiko Watanabe, Yasumasa Okamoto, Shigeru Morinobu, Hidenori Aizawa, Shigeto Yamawaki
Brain communications, 3, 4, fcab285, 2021, [International Magazine]
English, Scientific journal, Animals suffering from uncontrollable stress sometimes show low effort to escape stress (learned helplessness). Changes in serotonin (5-hydroxytryptamine) signalling are thought to underlie this behaviour. Although the release of 5-hydroxytryptamine is triggered by the action potential firing of dorsal raphe nuclei 5-hydroxytryptamine neurons, the electrophysiological changes induced by uncontrollable stress are largely unclear. Herein, we examined electrophysiological differences among 5-hydroxytryptamine neurons in naïve rats, learned helplessness rats and rats resistant to inescapable stress (non-learned helplessness). Five-week-old male Sprague Dawley rats were exposed to inescapable foot shocks. After an avoidance test session, rats were classified as learned helplessness or non-learned helplessness. Activity-dependent 5-hydroxytryptamine release induced by the administration of high-potassium solution was slower in free-moving learned helplessness rats. Subthreshold electrophysiological properties of 5-hydroxytryptamine neurons were identical among the three rat groups, but the depolarization-induced spike firing was significantly attenuated in learned helplessness rats. To clarify the underlying mechanisms, potassium (K+) channels regulating the spike firing were initially examined using naïve rats. K+ channels sensitive to 500 μM tetraethylammonium caused rapid repolarization of the action potential and the small conductance calcium-activated K+ channels produced afterhyperpolarization. Additionally, dendrotoxin-I, a blocker of Kv1.1 (encoded by Kcna1), Kv1.2 (encoded by Kcna2) and Kv1.6 (encoded by Kcna6) voltage-dependent K+ channels, weakly enhanced the spike firing frequency during depolarizing current injections without changes in individual spike waveforms in naïve rats. We found that dendrotoxin-I significantly enhanced the spike firing of 5-hydroxytryptamine neurons in learned helplessness rats. Consequently, the difference in spike firing among the three rat groups was abolished in the presence of dendrotoxin-I. These results suggest that the upregulation of dendrotoxin-I-sensitive Kv1 channels underlies the firing attenuation of 5-hydroxytryptamine neurons in learned helplessness rats. We also found that the antidepressant ketamine facilitated the spike firing of 5-hydroxytryptamine neurons and abolished the firing difference between learned helplessness and non-learned helplessness by suppressing dendrotoxin-I-sensitive Kv1 channels. The dendrotoxin-I-sensitive Kv1 channel may be a potential target for developing drugs to control activity of 5-hydroxytryptamine neurons. - Kv11 (ether-à-go-go-related gene) voltage-dependent K+ channels promote resonance and oscillation of subthreshold membrane potentials.
Toshinori Matsuoka, Miwako Yamasaki, Manabu Abe, Yukiko Matsuda, Hiroyuki Morino, Hideshi Kawakami, Kenji Sakimura, Masahiko Watanabe, Kouichi Hashimoto
The Journal of physiology, 599, 2, 547, 569, Jan. 2021, [International Magazine]
English, Scientific journal, KEY POINTS: Some ion channels are known to behave as inductors and make up the parallel resonant circuit in the plasma membrane of neurons, which enables neurons to respond to current inputs with a specific frequency (so-called 'resonant properties'). Here, we report that heterologous expression of mouse Kv11 voltage-dependent K+ channels generate resonance and oscillation at depolarized membrane potentials in HEK293 cells; expressions of individual Kv11 subtypes generate resonance and oscillation with different frequency properties. Kv11.3-expressing HEK293 cells exhibited transient conductance changes that opposed the current changes induced by voltage steps; this probably enables Kv11 channels to behave like an inductor. The resonance and oscillation of inferior olivary neurons were impaired at the resting membrane potential in Kv11.3 knockout mice. This study helps to elucidate basic ion channel properties that are crucial for the frequency responses of neurons. ABSTRACT: The plasma membranes of some neurons preferentially respond to current inputs with a specific frequency, and output as large voltage changes. This property is called resonance, and is thought to be mediated by ion channels that show inductor-like behaviour. However, details of the candidate ion channels remain unclear. In this study, we mainly focused on the functional roles of Kv11 potassium (K+ ) channels, encoded by ether-á-go-go-related genes, in resonance in mouse inferior olivary (IO) neurons. We transfected HEK293 cells with long or short splice variants of Kv11.1 (Merg1a and Merg1b) or Kv11.3, and examined membrane properties using whole-cell recording. Transfection with Kv11 channels reproduced resonance at membrane potentials depolarized from the resting state. Frequency ranges of Kv11.3-, Kv11.1(Merg1b)- and Kv11.1(Merg1a)-expressing cells were 2-6 Hz, 2-4 Hz, and 0.6-0.8 Hz, respectively. Responses of Kv11.3 currents to step voltage changes were essentially similar to those of inductor currents in the resistor-inductor-capacitor circuit. Furthermore, Kv11 transfections generated membrane potential oscillations. We also confirmed the contribution of HCN1 channels as a major mediator of resonance at more hyperpolarized potentials by transfection into HEK293 cells. The Kv11 current kinetics and properties of Kv11-dependent resonance suggested that Kv11.3 mediated resonance in IO neurons. This finding was confirmed by the impairment of resonance and oscillation at -30 to -60 mV in Kcnh7 (Kv11.3) knockout mice. These results suggest that Kv11 channels have important roles in inducing frequency-dependent responses in a subtype-dependent manner from resting to depolarized membrane potentials. - Development of an L-type Ca2+ channel-dependent Ca2+ transient during the radial migration of cortical excitatory neurons.
Shin-Ichiro Horigane, Shun Hamada, Satoshi Kamijo, Hirokazu Yamada, Miwako Yamasaki, Masahiko Watanabe, Haruhiko Bito, Toshihisa Ohtsuka, Sayaka Takemoto-Kimura
Neuroscience research, 169, 17, 26, 26 Jun. 2020, [International Magazine]
English, Scientific journal, Increasing evidence has shown that voltage-gated L-type Ca2+ channels (LTCCs) are crucial for neurodevelopmental events, including neuronal differentiation/migration and neurite morphogenesis/extension. However, the time course of their functional maturation during the development of excitatory neurons remains unknown. Using a combination of fluorescence in situ hybridization and in utero electroporation-based labeling, we found that the transcripts of Cacna1c and Cacna1d, which encode the LTCC pore-forming subunits, were upregulated in the intermediate zone (IZ) during radial migration. Ca2+ imaging using GCaMP6s in acute brain slices showed spontaneous Ca2+ transients in migrating neurons throughout the IZ. Neurons in the IZ upper layer, especially in the multipolar-to-bipolar transition layer (TL), exhibited more frequent Ca2+ transients than adjacent layers and responded to FPL64176, a potent activator of LTCC. Consistently, nimodipine, an LTCC blocker, inhibited spontaneous Ca2+ transients in neurons in the TL. Collectively, we showed a hitherto unknown increased prevalence of LTCC-dependent Ca2+ transients in the TL of the IZ upper layer during the radial migration of excitatory neurons, which could be essential for the regulation of Ca2+-dependent neurodevelopmental processes. - TMEM163 Regulates ATP-Gated P2X Receptor and Behavior.
Elizabeth J Salm, Patrick J Dunn, Lili Shan, Miwako Yamasaki, Nathalie M Malewicz, Taisuke Miyazaki, Joongkyu Park, Akio Sumioka, R Richard L Hamer, Wei-Wu He, Megumi Morimoto-Tomita, Robert H LaMotte, Susumu Tomita
Cell reports, 31, 9, 107704, 107704, 02 Jun. 2020, [International Magazine]
English, Scientific journal, Fast purinergic signaling is mediated by ATP and ATP-gated ionotropic P2X receptors (P2XRs), and it is implicated in pain-related behaviors. The properties exhibited by P2XRs vary between those expressed in heterologous cells and in vivo. Several modulators of ligand-gated ion channels have recently been identified, suggesting that there are P2XR functional modulators in vivo. Here, we establish a genome-wide open reading frame (ORF) collection and perform functional screening to identify modulators of P2XR activity. We identify TMEM163, which specifically modulates the channel properties and pharmacology of P2XRs. We also find that TMEM163 is required for full function of the neuronal P2XR and a pain-related ATP-evoked behavior. These results establish TMEM163 as a critical modulator of P2XRs in vivo and a potential target for the discovery of drugs for treating pain. - Nectin-2α is localized at cholinergic neuron dendrites and regulates synapse formation in the medial habenula.
Hajime Shiotani, Muneaki Miyata, Takeshi Kameyama, Kenji Mandai, Miwako Yamasaki, Masahiko Watanabe, Kiyohito Mizutani, Yoshimi Takai
The Journal of comparative neurology, 529, 2, 450, 477, 26 May 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, The medial habenula (MHb) receives afferents from the triangular septum and the medial septal complex, projects efferents to the interpeduncular nucleus (IPN) in the midbrain to regulate dopamine and serotonin levels, and is implicated in stress, depression, memory, and nicotine withdrawal syndrome. We previously showed that the cell adhesion molecule nectin-2α is localized at the boundary between adjacent somata of clustered cholinergic neurons and regulates the voltage-gated A-type K+ channel Kv4.2 localization at membrane specializations in the MHb. This adhesion apparatus, named nectin-2α spots, is not associated with the nectin-binding protein afadin or any classic cadherins and their binding proteins p120-catenin and β-catenin. We showed here that nectin-2α was additionally localized at cholinergic neuron dendrites in synaptic regions of the MHb. The genetic ablation of nectin-2 reduced the number of synapses in the MHb without affecting their morphology. Nectin-2α was associated with afadin, cadherin-8, p120-catenin, β-catenin, and αN-catenin, forming puncta adherentia junctions (PAJs). Nectin-2α was observed in the IPN, but not in the triangular septum or the medial septal complex. The genetic ablation of nectin-2 did not affect synapse formation in the IPN. These results indicate that nectin-2α forms two types of adhesion apparatus in the MHb, namely nectin-2α spots at neighboring somata and PAJs at neighboring dendrites, and that dendritic PAJs regulate synapse formation in the MHb. This article is protected by copyright. All rights reserved. - Expression mapping, quantification, and complex formation of GluD1 and GluD2 glutamate receptors in adult mouse brain.
Chihiro Nakamoto, Kohtarou Konno, Taisuke Miyazaki, Ena Nakatsukasa, Rie Natsume, Manabu Abe, Meiko Kawamura, Yugo Fukazawa, Ryuichi Shigemoto, Miwako Yamasaki, Kenji Sakimura, Masahiko Watanabe
The Journal of comparative neurology, 528, 6, 1003, 1027, Apr. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, In the cerebellum, GluD2 is exclusively expressed in Purkinje cells, where it regulates synapse formation and regeneration, synaptic plasticity, and motor learning. Delayed cognitive development in humans with GluD2 gene mutations suggests extracerebellar functions of GluD2. However, extracerebellar expression of GluD2 and its relationship with that of GluD1 are poorly understood. GluD2 mRNA and protein were widely detected, with relatively high levels observed in the olfactory glomerular layer, medial prefrontal cortex, cingulate cortex, retrosplenial granular cortex, olfactory tubercle, subiculum, striatum, lateral septum, anterodorsal thalamic nucleus, and arcuate hypothalamic nucleus. These regions were also enriched for GluD1, and many individual neurons coexpressed the two GluDs. In the retrosplenial granular cortex, GluD1 and GluD2 were selectively expressed at PSD-95-expressing glutamatergic synapses, and their coexpression on the same synapses was shown by SDS-digested freeze-fracture replica labeling. Biochemically, GluD1 and GluD2 formed coimmunoprecipitable complex formation in HEK293T cells and in the cerebral cortex and hippocampus. We further estimated the relative protein amount by quantitative immunoblotting using GluA2/GluD2 and GluA2/GluD1 chimeric proteins as standards for titration of GluD1 and GluD2 antibodies. Intriguingly, the relative amount of GluD2 was almost comparable to that of GluD1 in the postsynaptic density fraction prepared from the cerebral cortex and hippocampus. In contrast, GluD2 was overwhelmingly predominant in the cerebellum. Thus, we have determined the relative extracerebellar expression of GluD1 and GluD2 at regional, neuronal, and synaptic levels. These data provide a molecular-anatomical basis for possible competitive and cooperative interactions of GluD family members at synapses in various brain regions. - Localization of phospholipase C β3 in the major salivary glands of adult mice.
Atsara Rawangwong, Atthapon Pidsaya, Wipawee Thoungseabyoun, Apussara Tachow, Tarinee Sawatpanich, Waraporn Sakaew, Miwako Yamasaki, Masahiko Watanabe, Hisatake Kondo, Wiphawi Hipkaeo
Acta histochemica, 121, 4, 484, 490, May 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Phospholipase C (PLC)β has a role in saliva secretion by controlling intracellular Ca2+via its product, IP3. The present study was attempted to localize PLCβ isoforms in mouse salivary glands in situ. A single major band was detected for PLCβ3 in immunoblots of the parotid and sublingual glands (PG, SLG), while no such band was seen in the submandibular gland (SMG). No bands were detected for PLCβ1 or 4 in the three glands. In immuno-light microscopy of PG and SLG, substantial immunoreactivity for PLCβ3 was seen in the cytoplasm including the plasmalemma of almost all ductal cells, while no distinct immunoreactivity was discerned in most acinar cells except for sublingual demilune cells. Numerous ductal cells exhibited higher immunoreactivity for PLCβ3 in their apical/supranuclear cell domain including the plasmalemma than in the basal/infranuclear domain, indicating an apico-basal polarity. In immuno-gold electron microscopy of PG ducts and SLG ducts and demilunes, most gold particles were found in association with plasma membranes as well as various intracellular membranes, most of which formed small oblong or flattened vesicles and vacuoles. A few particles were seen without association with any membranous structures. The present finding supports the previous physio-pharmacological result that Ca2+-signaling proteins as well as initial intracellular Ca2+ changes occur in the apical cell domain including the plasma membranes of the exocrine cells. - mGluR1 in cerebellar Purkinje cells is essential for the formation but not expression of associative eyeblink memory.
Nakao H, Kishimoto Y, Hashimoto K, Kitamura K, Yamasaki M, Nakao K, Watanabe M, Kano M, Kirino Y, Aiba A
Scientific reports, 9, 1, 7353, 7353, May 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Classical eyeblink conditioning is a representative associative motor learning that requires both the cerebellar cortex and the deep cerebellar nucleus (DCN). Metabotropic glutamate receptor subtype 1 (mGluR1) is richly expressed in Purkinje cells (PCs) of the cerebellar cortex. Global mGluR1 knock-out (KO) mice show a significantly lower percentage of conditioned response (CR%) than wild-type mice in eyeblink conditioning, and the impaired CR% is restored by the introduction of mGluR1 in PCs. However, the specific roles of mGluR1 in major memory processes, including formation, storage and expression have not yet been defined. We thus examined the role of mGluR1 in these processes of eyeblink conditioning, using mGluR1 conditional KO (cKO) mice harboring a selective and reversible expression of mGluR1 in PCs. We have found that eyeblink memory is not latently formed in the absence of mGluR1 in adult mouse PCs. However, once acquired, eyeblink memory is expressed even after the depletion of mGluR1 in PCs. We thus conclude that mGluR1 in PCs is indispensable for the formation of eyeblink memory, while it is not required for the expression of CR. - Heterogeneous localization of muscarinic cholinoceptor M1 in the salivary ducts of adult mice.
Atsara Rawangwong, Suthankamon Khrongyut, Surang Chomphoo, Kohtaro Konno, Miwako Yamasaki, Masahiko Watanabe, Hisatake Kondo, Wiphawi Hipkaeo
Archives of oral biology, 100, 14, 22, Apr. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, We hypothesize variation in expression and localization, along the course of the glandular tubule, of muscarinic cholinergic receptor M1 which plays as a distinct contribution, though minor in comparison with M3 receptor, in saliva secretion. Localization of the M1 receptor was examined using immunohistochemistry in three major salivary glands. Although all glandular cells were more or less M1-immunoreactive, acinar cells were weakly immunoreactive, while ductal cells exhibited substantial M1-immunoreactivity. Many ductal cells exhibited clear polarity with higher immunoreactivity in their apical/supra-nuclear domain. However, some exhibited indistinct polarity because of additional higher immunoreactivity in their basal/infra-nuclear domain. A small group of cells with intense immunoreactivity was found, mostly located in the intercalated ducts or in portions of the striated ducts close to the intercalated ducts. In immuno-electron microscopy, the immunoreactive materials were mainly in the cytoplasm including various vesicles and vacuoles. Unexpectedly, distinct immunoreactivity on apical and basal plasma membranes was infrequent in most ductal cells. The heterogeneous localization of M1-immunoreactivity along the gland tubular system is discussed in view of possible modulatory roles of the M1 receptor in saliva secretion. - Silent Learning.
Janine I Rossato, Andrea Moreno, Lisa Genzel, Miwako Yamasaki, Tomonori Takeuchi, Santiago Canals, Richard G M Morris
Current biology : CB, 28, 21, 3508, 3515, 05 Nov. 2018, [International Magazine]
English, Scientific journal, We introduce the concept of "silent learning"-the capacity to learn despite neuronal cell-firing being largely absent. This idea emerged from thinking about dendritic computation [1, 2] and examining whether the encoding, expression, and retrieval of hippocampal-dependent memory could be dissociated using the intrahippocampal infusion of pharmacological compounds. We observed that very modest enhancement of GABAergic inhibition with low-dose muscimol blocked both cell-firing and the retrieval of an already-formed memory but left induction of long-term potentiation (LTP) and new spatial memory encoding intact (silent learning). In contrast, blockade of hippocampal NMDA receptors by intrahippocampal D-AP5 impaired both the induction of LTP and encoding but had no effect on memory retrieval. Blockade of AMPA receptors by CNQX impaired excitatory synaptic transmission and cell-firing and both memory encoding and retrieval. Thus, in keeping with the synaptic plasticity and memory hypothesis [3], the hippocampal network can mediate new memory encoding when LTP induction is intact even under conditions in which somatic cell-firing is blocked. - Localization of nectin-2α at the boundary between the adjacent somata of the clustered cholinergic neurons and its regulatory role in the subcellular localization of the voltage-gated A-type K+ channel Kv4.2 in the medial habenula
Hajime Shiotani, Muneaki Miyata, Yu Itoh, Shujie Wang, Aika Kaito, Akira Mizoguchi, Miwako Yamasaki, Masahiko Watanabe, Kenji Mandai, Hideki Mochizuki, Yoshimi Takai
Journal of Comparative Neurology, 526, 9, 1527, 1549, Wiley-Liss Inc., 15 Jun. 2018, [Peer-reviewed]
English, Scientific journal - Olig2-Lineage astrocytes: A distinct subtype of astrocytes that differs from GFAP astrocytes
Kouko Tatsumi, Ayami Isonishi, Miwako Yamasaki, Yoshie Kawabe, Shoko Morita-Takemura, Kazuki Nakahara, Yuki Terada, Takeaki Shinjo, Hiroaki Okuda, Tatsuhide Tanaka, Akio Wanaka
Frontiers in Neuroanatomy, 12, 8, 8, Frontiers Media S.A., 14 Feb. 2018, [Peer-reviewed]
English, Scientific journal - Serotonergic Input to Orexin Neurons Plays a Role in Maintaining Wakefulness and REM Sleep Architecture.
Saito YC, Tsujino N, Abe M, Yamazaki M, Sakimura K, Sakurai T
Frontiers in neuroscience, 12, 892, 2018, [Peer-reviewed] - Localization of photoperiod responsive circadian oscillators in the mouse suprachiasmatic nucleus
Tomoko Yoshikawa, Natsuko F. Inagaki, Seiji Takagi, Shigeru Kuroda, Miwako Yamasaki, Masahiko Watanabe, Sato Honma, Ken-ichi Honma
SCIENTIFIC REPORTS, 7, 1, 8210, Aug. 2017, [Peer-reviewed]
English, Scientific journal - Glutamate transporter GLAST controls synaptic wrapping by Bergmann glia and ensures proper wiring of Purkinje cells
Taisuke Miyazaki, Miwako Yamasaki, Kouichi Hashimoto, Kazuhisa Kohda, Michisuke Yuzaki, Keiko Shimamoto, Kohichi Tanaka, Masanobu Kano, Masahiko Watanabe
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 114, 28, 7438, 7443, Jul. 2017, [Peer-reviewed]
English, Scientific journal - Locus Coeruleus and Dopamine-Dependent Memory Consolidation
Miwako Yamasaki, Tomonori Takeuchi
NEURAL PLASTICITY, 2017, 8602690, 2017, [Peer-reviewed], [Lead author, Corresponding author]
English - QRFP-Deficient Mice Are Hypophagic, Lean, Hypoactive and Exhibit Increased Anxiety-Like Behavior
Kitaro Okamoto, Miwako Yamasaki, Keizo Takao, Shingo Soya, Monica Iwasaki, Koh Sasaki, Kenta Magoori, Iori Sakakibara, Tsuyoshi Miyakawa, Michihiro Mieda, Masahiko Watanabe, Juro Sakai, Masashi Yanagisawa, Takeshi Sakurai
PLOS ONE, 11, 11, e0164716, Nov. 2016, [Peer-reviewed]
English, Scientific journal - The active zone protein CAST regulates synaptic vesicle recycling and quantal size in the mouse hippocampus
Shizuka Kobayashi, Yamato Hida, Hiroyoshi Ishizaki, Eiji Inoue, Miki Tanaka-Okamoto, Miwako Yamasaki, Taisuke Miyazaki, Masahiro Fukaya, Isao Kitajima, Yoshimi Takai, Masahiko Watanabe, Toshihisa Ohtsuka, Toshiya Manabe
EUROPEAN JOURNAL OF NEUROSCIENCE, 44, 5, 2272, 2284, Sep. 2016, [Peer-reviewed]
English, Scientific journal - Locus coeruleus and dopaminergic consolidation of everyday memory
Tomonori Takeuchi, Adrian J. Duszkiewicz, Alex Sonneborn, Patrick A. Spooner, Miwako Yamasaki, Masahiko Watanabe, Caroline C. Smith, Guillen Fernandez, Karl Deisseroth, Robert W. Greene, Richard G. M. Morris
NATURE, 537, 7620, 357, +, Sep. 2016, [Peer-reviewed]
English, Scientific journal - Crucial Roles of the Endocannabinoid 2-Arachidonoylglycerol in the Suppression of Epileptic Seizures.
Sugaya Y, Yamazaki M, Uchigashima M, Kobayashi K, Watanabe M, Sakimura K, Kano M
Cell reports, 16, 5, 1405, 1415, Aug. 2016, [Peer-reviewed] - Distinct Subunit Domains Govern Synaptic Stability and Specificity of the Kainate Receptor
Christoph Straub, Yoav Noam, Toshihiro Nomura, Miwako Yamasaki, Dan Yan, Herman B. Fernandes, Ping Zhang, James R. Howe, Masahiko Watanabe, Anis Contractor, Susumu Tomita
CELL REPORTS, 16, 2, 531, 544, Jul. 2016, [Peer-reviewed]
English, Scientific journal - Ionic Basis for Membrane Potential Resonance in Neurons of the Inferior Olive
Yoshiko Matsumoto-Makidono, Hisako Nakayama, Miwako Yamasaki, Taisuke Miyazaki, Kazuto Kobayashi, Masahiko Watanabe, Masanobu Kano, Kenji Sakimura, Kouichi Hashimoto
CELL REPORTS, 16, 4, 994, 1004, Jul. 2016, [Peer-reviewed]
English, Scientific journal - Developmental Switch in Spike Timing-Dependent Plasticity and Cannabinoid-Dependent Reorganization of the Thalamocortical Projection in the Barrel Cortex
Chiaki Itami, Jui-Yen Huang, Miwako Yamasaki, Masahiko Watanabe, Hui-Chen Lu, Fumitaka Kimura
JOURNAL OF NEUROSCIENCE, 36, 26, 7039, 7054, Jun. 2016, [Peer-reviewed]
English, Scientific journal - Transsynaptic Modulation of Kainate Receptor Functions by C1q-like Proteins
Keiko Matsuda, Timotheus Budisantoso, Nikolaos Mitakidis, Yuki Sugaya, Eriko Miura, Wataru Kakegawa, Miwako Yamasaki, Kohtarou Konno, Motokazu Uchigashima, Manabu Abe, Izumi Watanabe, Masanobu Kano, Masahiko Watanabe, Kenji Sakimura, A. Radu Aricescu, Michisuke Yuzaki
NEURON, 90, 4, 752, 767, May 2016, [Peer-reviewed]
English, Scientific journal - TARP gamma-2 and gamma-8 Differentially Control AMPAR Density Across Schaffer Collateral/Commissural Synapses in the Hippocampal CA1 Area
Miwako Yamasaki, Masahiro Fukaya, Maya Yamazaki, Hirotsugu Azechi, Rie Natsume, Manabu Abe, Kenji Sakimura, Masahiko Watanabe
JOURNAL OF NEUROSCIENCE, 36, 15, 4296, 4312, Apr. 2016, [Peer-reviewed], [Lead author]
English, Scientific journal - Territories of heterologous inputs onto Purkinje cell dendrites are segregated by mGluR1-dependent parallel fiber synapse elimination
Ryoichi Ichikawa, Kouichi Hashimoto, Taisuke Miyazaki, Motokazu Uchigashima, Miwako Yamasaki, Atsu Aiba, Masanobu Kano, Masahiko Watanabe
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 113, 8, 2282, 2287, Feb. 2016, [Peer-reviewed]
English, Scientific journal - Molecular and anatomical evidence for the input pathway- and target cell type-dependent regulation of glutamatergic synapses
Miwako Yamasaki
ANATOMICAL SCIENCE INTERNATIONAL, 91, 1, 8, 21, Jan. 2016, [Peer-reviewed], [Lead author, Corresponding author]
English - VGluT3-Expressing CCK-Positive Basket Cells Construct Invaginating Synapses Enriched with Endocannabinoid Signaling Proteins in Particular Cortical and Cortex-Like Amygdaloid Regions of Mouse Brains
Yuki Omiya, Motokazu Uchigashima, Kohtarou Konno, Miwako Yamasaki, Taisuke Miyazaki, Takayuki Yoshida, Ichiro Kusumi, Masahiko Watanabe
JOURNAL OF NEUROSCIENCE, 35, 10, 4215, 4228, Mar. 2015, [Peer-reviewed]
English, Scientific journal - Involvement of diacylglycerol kinase beta in the spine formation at distal dendrites of striatal medium spiny neurons
Yasukazu Hozumi, Kenichi Kakefuda, Miwako Yamasaki, Masahiko Watanabe, Hideaki Hara, Kaoru Goto
BRAIN RESEARCH, 1594, 36, 45, Jan. 2015, [Peer-reviewed]
English, Scientific journal - The glutamate receptor GluN2 subunit regulates synaptic trafficking of AMPA receptors in the neonatal mouse brain
Shun Hamada, Itone Ogawa, Miwako Yamasaki, Yuji Kiyama, Hidetoshi Kassai, Ayako M. Watabe, Kazuki Nakao, Atsu Aiba, Masahiko Watanabe, Toshiya Manabe
EUROPEAN JOURNAL OF NEUROSCIENCE, 40, 8, 3136, 3146, Oct. 2014, [Peer-reviewed]
English, Scientific journal - Neuron type- and input pathway-dependent expression of Slc4a10 in adult mouse brains
Xiaohong Song, Miwako Yamasaki, Taisuke Miyazaki, Kohtarou Konno, Motokazu Uchigashima, Masahiko Watanabe
EUROPEAN JOURNAL OF NEUROSCIENCE, 40, 5, 2797, 2810, Sep. 2014, [Peer-reviewed]
English, Scientific journal - Global Scaling Down of Excitatory Postsynaptic Responses in Cerebellar Purkinje Cells Impairs Developmental Synapse Elimination
Shinya Kawata, Taisuke Miyazaki, Maya Yamazaki, Takayasu Mikuni, Miwako Yamasaki, Kouichi Hashimoto, Masahiko Watanabe, Kenji Sakimura, Masanobu Kano
CELL REPORTS, 8, 4, 1119, 1129, Aug. 2014, [Peer-reviewed]
English, Scientific journal - Opposing Role of NMDA Receptor GluN2B and GluN2D in Somatosensory Development and Maturation
Miwako Yamasaki, Rieko Okada, Chihiro Takasaki, Shima Toki, Masahiro Fukaya, Rie Natsume, Kenji Sakimura, Masayoshi Mishina, Tetsuo Shirakawa, Masahiko Watanabe
JOURNAL OF NEUROSCIENCE, 34, 35, 11534, 11548, Aug. 2014, [Peer-reviewed], [Lead author]
English, Scientific journal - Enriched Expression of GluD1 in Higher Brain Regions and Its Involvement in Parallel Fiber-Interneuron Synapse Formation in the Cerebellum
Kohtarou Konno, Keiko Matsuda, Chihiro Nakamoto, Motokazu Uchigashima, Taisuke Miyazaki, Miwako Yamasaki, Kenji Sakimura, Michisuke Yuzaki, Masahiko Watanabe
JOURNAL OF NEUROSCIENCE, 34, 22, 7412, 7424, May 2014, [Peer-reviewed]
English, Scientific journal - Protocadherin 17 Regulates Presynaptic Assembly in Topographic Corticobasal Ganglia Circuits
Naosuke Hoshina, Asami Tanimura, Miwako Yamasaki, Takeshi Inoue, Ryoji Fukabori, Teiko Kuroda, Kazumasa Yokoyama, Tohru Tezuka, Hiroshi Sagara, Shinji Hirano, Hiroshi Kiyonari, Masahiko Takada, Kazuto Kobayashi, Masahiko Watanabe, Masanobu Kano, Takanobu Nakazawa, Tadashi Yamamoto
NEURON, 78, 5, 839, 854, Jun. 2013, [Peer-reviewed]
English, Scientific journal - Homeostatic Control of Synaptic Transmission by Distinct Glutamate Receptors
Dan Yan, Miwako Yamasaki, Christoph Straub, Masahiko Watanabe, Susumu Tomita
NEURON, 78, 4, 687, 699, May 2013, [Peer-reviewed]
English, Scientific journal - Type 2K+Cl cotransporter is preferentially recruited to climbing fiber synapses during development and the stellate cell-targeting dendritic zone at adulthood in cerebellar Purkinje cells
Issei Kawakita, Motokazu Uchigashima, Kohtarou Konno, Taisuke Miyazaki, Miwako Yamasaki, Masahiko Watanabe
EUROPEAN JOURNAL OF NEUROSCIENCE, 37, 4, 532, 543, Feb. 2013, [Peer-reviewed]
English, Scientific journal - Autoantibodies to epilepsy-related LGI1 in limbic encephalitis neutralize LGI1-ADAM22 interaction and reduce synaptic AMPA receptors
Toshika Ohkawa, Yuko Fukata, Miwako Yamasaki, Taisuke Miyazaki, Norihiko Yokoi, Hiroshi Takashima, Masahiko Watanabe, Osamu Watanabe, Masaki Fukata
Journal of Neuroscience, 33, 46, 18161, 18174, 2013, [Peer-reviewed]
English, Scientific journal - Difference in synaptic strengths among competing inputs and absolute synaptic strengths contribute to distinct phase of climbing fiber synapse development in cerebellum
Kawata Shinya, Hashimoto Kouichi, Yamazaki Maya, Miyazaki Taisuke, Yamasaki Miwako, Mikuni Takayasu, Watanabe Masahiko, Sakimura Kenji, Kano Masanobu
JOURNAL OF PHYSIOLOGICAL SCIENCES, 63, S188, 2013, [Peer-reviewed] - Three Types of Neurochemical Projection from the Bed Nucleus of the Stria Terminalis to the Ventral Tegmental Area in Adult Mice
Takehiro Kudo, Motokazu Uchigashima, Taisuke Miyazaki, Kohtarou Konno, Miwako Yamasaki, Yuchio Yanagawa, Masabumi Minami, Masahiko Watanabe
JOURNAL OF NEUROSCIENCE, 32, 50, 18035, 18046, Dec. 2012, [Peer-reviewed]
English, Scientific journal - Distinct Neurochemical and Functional Properties of GAD67-Containing 5-HT Neurons in the Rat Dorsal Raphe Nucleus
Hiroki Shikanai, Takayuki Yoshida, Kohtarou Konno, Miwako Yamasaki, Takeshi Izumi, Yu Ohmura, Masahiko Watanabe, Mitsuhiro Yoshioka
JOURNAL OF NEUROSCIENCE, 32, 41, 14415, 14426, Oct. 2012, [Peer-reviewed]
English, Scientific journal - Lack of Molecular-Anatomical Evidence for GABAergic Influence on Axon Initial Segment of Cerebellar Purkinje Cells by the Pinceau Formation
Atsushi Iwakura, Motokazu Uchigashima, Taisuke Miyazaki, Miwako Yamasaki, Masahiko Watanabe
JOURNAL OF NEUROSCIENCE, 32, 27, 9438, 9448, Jul. 2012, [Peer-reviewed]
English, Scientific journal - Rewiring of Afferent Fibers in the Somatosensory Thalamus of Mice Caused by Peripheral Sensory Nerve Transection
Yuichi Takeuchi, Miwako Yamasaki, Yasuyuki Nagumo, Keiji Imoto, Masahiko Watanabe, Mariko Miyata
JOURNAL OF NEUROSCIENCE, 32, 20, 6917, 6930, May 2012, [Peer-reviewed]
English, Scientific journal - Ca(v)2.1 in Cerebellar Purkinje Cells Regulates Competitive Excitatory Synaptic Wiring, Cell Survival, and Cerebellar Biochemical Compartmentalization
Taisuke Miyazaki, Miwako Yamasaki, Kouichi Hashimoto, Maya Yamazaki, Manabu Abe, Hiroshi Usui, Masanobu Kano, Kenji Sakimura, Masahiko Watanabe
JOURNAL OF NEUROSCIENCE, 32, 4, 1311, 1328, Jan. 2012, [Peer-reviewed]
English, Scientific journal - Developmental Switching of Perisomatic Innervation from Climbing Fibers to Basket Cell Fibers in Cerebellar Purkinje Cells
Ryoichi Ichikawa, Miwako Yamasaki, Taisuke Miyazaki, Kohtarou Konno, Kouichi Hashimoto, Haruyuki Tatsumi, Yoshiro Inoue, Masanobu Kano, Masahiko Watanabe
JOURNAL OF NEUROSCIENCE, 31, 47, 16916, 16927, Nov. 2011, [Peer-reviewed]
English, Scientific journal - Orexin Neurons Receive Glycinergic Innervations
Mari Hondo, Naoki Furutani, Miwako Yamasaki, Masahiko Watanabe, Takeshi Sakurai
PLOS ONE, 6, 9, e25076, Sep. 2011, [Peer-reviewed], [Lead author]
English, Scientific journal - Distinct functions of kainate receptors in the brain are determined by the auxiliary subunit Neto1
Christoph Straub, David L. Hunt, Miwako Yamasaki, Kwang S. Kim, Masahiko Watanabe, Pablo E. Castillo, Susumu Tomita
NATURE NEUROSCIENCE, 14, 7, 866, U83, Jul. 2011, [Peer-reviewed]
English, Scientific journal - Molecular and Morphological Configuration for 2-Arachidonoylglycerol-Mediated Retrograde Signaling at Mossy Cell-Granule Cell Synapses in the Dentate Gyrus
Motokazu Uchigashima, Maya Yamazaki, Miwako Yamasaki, Asami Tanimura, Kenji Sakimura, Masanobu Kano, Masahiko Watanabe
JOURNAL OF NEUROSCIENCE, 31, 21, 7700, 7714, May 2011, [Peer-reviewed]
English, Scientific journal - Glutamate Receptor delta 2 Is Essential for Input Pathway-Dependent Regulation of Synaptic AMPAR Contents in Cerebellar Purkinje Cells
Miwako Yamasaki, Taisuke Miyazaki, Hirotsugu Azechi, Manabu Abe, Rie Natsume, Teruki Hagiwara, Atsu Aiba, Masayoshi Mishina, Kenji Sakimura, Masahiko Watanabe
JOURNAL OF NEUROSCIENCE, 31, 9, 3362, 3374, Mar. 2011, [Peer-reviewed], [Lead author]
English, Scientific journal - Unique inhibitory synapse with particularly rich endocannabinoid signaling machinery on pyramidal neurons in basal amygdaloid nucleus
Takayuki Yoshida, Motokazu Uchigashima, Miwako Yamasaki, Istvan Katona, Maya Yamazaki, Kenji Sakimura, Masanobu Kano, Mitsuhiro Yoshioka, Masahiko Watanabe
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 108, 7, 3059, 3064, Feb. 2011, [Peer-reviewed]
English, Scientific journal - Inositol 1,4,5-trisphosphate signaling maintains the activity of glutamate uptake in Bergmann glia
Okubo Yohei, Mashimo Masato, Yamazawa Toshiko, Yamasaki Miwako, Watanabe Masahiko, Murayama Toshihiko, Iino Masamitsu
NEUROSCIENCE RESEARCH, 71, E327, 2011, [Peer-reviewed] - Invaginating inhibitory synapse with particularly rich endocannabinoid signaling machinery in the basal nucleus of the amygdala
Yoshida Takayuki, Uchigashima Motokazu, Yamasaki Miwako, Katona Istvan, Yamazaki Maya, Sakimura Kenji, Kano Masanobu, Yoshioka Mitsuhiro, Watanabe Masahiko
NEUROSCIENCE RESEARCH, 71, E93, E94, 2011, [Peer-reviewed] - Glutamate receptor delta 2 is essential for input pathway-dependent regulation of synaptic AMPAR contents in cerebellar Purkinje cells
Yamasaki Miwako, Miyazaki Taisuke, Azechi Hirotsugu, Abe Manabu, Natsume Rie, Hagiwara Teruki, Aiba Atsu, Mishina Masayoshi, Sakimura Kenji, Watanabe Masahiko
NEUROSCIENCE RESEARCH, 71, E93, 2011, [Peer-reviewed] - Neurochemical characterization of neurons in the bed nucleus of the stria terminalis projecting to the ventral tegmental area
Kudo Takehiro, Uchigashima Motokazu, Miyazaki Taisuke, Yamasaki Miwako, Minami Masabumi, Watanabe Masahiko
NEUROSCIENCE RESEARCH, 71, E322, 2011, [Peer-reviewed] - Glycinergic regulation of orexin neurons
Hondo Mari, Furutani Naoki, Yamasaki Miwako, Watanabe Masahiko, Sakurai Takeshi
NEUROSCIENCE RESEARCH, 71, E170, 2011, [Peer-reviewed] - Cellular expression and subcellular localization of secretogranin II in the mouse hippocampus and cerebellum
Taisuke Miyazaki, Miwako Yamasaki, Motokazu Uchigashima, Ayano Matsushima, Masahiko Watanabe
EUROPEAN JOURNAL OF NEUROSCIENCE, 33, 1, 82, 94, Jan. 2011, [Peer-reviewed]
English, Scientific journal - Inositol 1,4,5-trisphosphate signaling maintains the activity of glutamate uptake in Bergmann glia
Masato Mashimo, Yohei Okubo, Toshiko Yamazawa, Miwako Yamasaki, Masahiko Watanabe, Toshihiko Murayama, Masamitsu Iino
EUROPEAN JOURNAL OF NEUROSCIENCE, 32, 10, 1668, 1677, Nov. 2010, [Peer-reviewed]
English, Scientific journal - Ablation of Glutamate Receptor GluR delta 2 in Adult Purkinje Cells Causes Multiple Innervation of Climbing Fibers by Inducing Aberrant Invasion to Parallel Fiber Innervation Territory
Taisuke Miyazaki, Miwako Yamasaki, Tomonori Takeuchi, Kenji Sakimura, Masayoshi Mishina, Masahiko Watanabe
JOURNAL OF NEUROSCIENCE, 30, 45, 15196, 15209, Nov. 2010, [Peer-reviewed]
English, Scientific journal - Cytochemical and cytological properties of perineuronal oligodendrocytes in the mouse cortex.
Takasaki C, Yamasaki M, Uchigashima M, Konno K, Yanagawa Y, Watanabe M
The European journal of neuroscience, 32, 8, 1326, 1336, Oct. 2010, [Peer-reviewed]
English - TARPs gamma-2 and gamma-7 are essential for AMPA receptor expression in the cerebellum
Maya Yamazaki, Masahiro Fukaya, Kouichi Hashimoto, Miwako Yamasaki, Mika Tsujita, Makoto Itakura, Manabu Abe, Rie Natsume, Masami Takahashi, Masanobu Kano, Kenji Sakimura, Masahiko Watanabe
EUROPEAN JOURNAL OF NEUROSCIENCE, 31, 12, 2204, 2220, Jun. 2010, [Peer-reviewed]
English, Scientific journal - Imaging extrasynaptic glutamate dynamics in the brain
Yohei Okubo, Hiroshi Sekiya, Shigeyuki Namiki, Hirokazu Sakamoto, Sho Iinuma, Miwako Yamasaki, Masahiko Watanabe, Kenzo Hirose, Masamitsu Iino
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 107, 14, 6526, 6531, Apr. 2010, [Peer-reviewed]
English, Scientific journal - Preferential Localization of Muscarinic M-1 Receptor on Dendritic Shaft and Spine of Cortical Pyramidal Cells and Its Anatomical Evidence for Volume Transmission
Miwako Yamasaki, Minoru Matsui, Masahiko Watanabe
JOURNAL OF NEUROSCIENCE, 30, 12, 4408, 4418, Mar. 2010, [Peer-reviewed], [Lead author]
English, Scientific journal - Spatiotemporal dynamics of glutamate spillover
Okubo Yohei, Sekiya Hiroshi, Namiki Shigeyuki, Sakamoto Hirokazu, Iinuma Sho, Yamasaki Miwako, Watanabe Masahiko, Hirose Kenzo, Iino Masamitsu
JOURNAL OF PHARMACOLOGICAL SCIENCES, 112, 110P, 2010, [Peer-reviewed] - Ablation of glutamate receptor GluD2 in adult Purkinje cells causes multiple innervation of climbing fibers by ectopic innervation of transverse collaterals
Miyazaki Taisuke, Yamasaki Miwako, Takeuchi Tomonori, Sakimura Kenji, Mishina Masayoshi, Watanabe Masahiko
NEUROSCIENCE RESEARCH, 68, E86, 2010, [Peer-reviewed] - TARPs gamma-2 and gamma-7 are functional components of cerebellar AMPA receptor
Yamazaki Maya, Fukaya Masahiro, Hashimoto Kouichi, Yamasaki Miwako, Itakura Makoto, Takahashi Masami, Kano Masanobu, Watanabe Masahiko, Sakimura Kenji
NEUROSCIENCE RESEARCH, 68, E223, E224, 2010, [Peer-reviewed] - Synaptic localization and content of four AMPA receptor subunits at excitatory hippocampal synapses
Yamasaki Miwako, Fukaya Masahiro, Abe Manabu, Sakimura Kenji, Watanabe Masahiko
NEUROSCIENCE RESEARCH, 68, E56, 2010, [Peer-reviewed] - Lentiviral vector-mediated rescue of motor behavior in spontaneously occurring hereditary ataxic mice
Akira Iizuka, Kiyohiko Takayama, Takashi Torashima, Miwako Yamasaki, Chiho Koyama, Kazuhiro Mitsumura, Masahiko Watanabe, Hirozaku Hirai
NEUROBIOLOGY OF DISEASE, 35, 3, 457, 465, Sep. 2009, [Peer-reviewed]
English, Scientific journal - NMDA Receptor GluN2B (GluR epsilon 2/NR2B) Subunit Is Crucial for Channel Function, Postsynaptic Macromolecular Organization, and Actin Cytoskeleton at Hippocampal CA3 Synapses
Kaori Akashi, Toshikazu Kakizaki, Haruyuki Kamiya, Masahiro Fukaya, Miwako Yamasaki, Manabu Abe, Rie Natsume, Masahiko Watanabe, Kenji Sakimura
JOURNAL OF NEUROSCIENCE, 29, 35, 10869, 10882, Sep. 2009, [Peer-reviewed]
English, Scientific journal - Rescue of abnormal phenotypes in delta 2 glutamate receptor-deficient mice by the extracellular N-terminal and intracellular C-terminal domains of the delta 2 glutamate receptor
Takashi Torashima, Akira Iizuka, Hajime Horiuchi, Kazuhiro Mitsumura, Miwako Yamasaki, Chiho Koyama, Kiyohiko Takayama, Masae Iino, Masahiko Watanabe, Hirozaku Hirai
EUROPEAN JOURNAL OF NEUROSCIENCE, 30, 3, 355, 365, Aug. 2009, [Peer-reviewed]
English, Scientific journal - GLAST IS ESSENTIAL FOR CYTOLOGICAL DIFFERENTIATION OF BERGMANN GLIA AND CLIMBING FIBER MONOINNERVATION BY SUPPRESSING ECTOPIC INNERVATION
Miyazaki Taisuke, Yamasaki Miwako, Tanaka Kouichi, Watanabe Masahiko
JOURNAL OF PHYSIOLOGICAL SCIENCES, 59, 198, 2009, [Peer-reviewed] - Imaging extrasynaptic glutamate dynamics in the brain
Okubo Yohei, Sekiya Hiroshi, Namiki Shigeyuki, Sakamoto Hirokazu, Iinuma Sho, Yamasaki Miwako, Watanabe Masahiko, Hirose Kenzo, Iino Masamitsu
NEUROSCIENCE RESEARCH, 65, S142, S143, 2009, [Peer-reviewed] - GluR epsilon 2 subunit is crucial for NMDA receptor activity and regulation of postsynaptic macromolecular organization
Akashi Kaori, Kakizaki Toshikazu, Kamiya Haruyuki, Fukaya Masahiro, Yamasaki Miwako, Abe Manabu, Watanabe Masahiko, Sakimura Kenji
NEUROSCIENCE RESEARCH, 65, S139, S140, 2009, [Peer-reviewed] - PREFERENTIAL EXPRESSION OF M1 mAChR IN DENDRITES AND SPINES OF CORTICAL PRINCIPAL CELLS AND ITS ANATOMICAL EVIDENCE FOR VOLUME TRANSMISSION
Miwako Yamasaki, Masahiko Watanabe
JOURNAL OF PHYSIOLOGICAL SCIENCES, 59, 142, 142, 2009, [Peer-reviewed]
English - Use-dependent amplification of presynaptic Ca2+ signaling by axonal ryanodine receptors at the hippocampal mossy fiber synapse
Hidemi Shimizu, Masahiro Fukaya, Miwako Yamasaki, Masahiko Watanabe, Toshiya Manabe, Haruyuki Kamiya
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 105, 33, 11998, 12003, Aug. 2008, [Peer-reviewed]
English, Scientific journal - Glutamate transporters regulate lesion-induced plasticity in the developing somatosensory cortex
Chihiro Takasaki, Rieko Okada, Akira Mitani, Masahiro Fukaya, Miwako Yamasaki, Yuri Fujihara, Tetsuo Shirakawa, Kohichi Tanaka, Masahiko Watanabe
JOURNAL OF NEUROSCIENCE, 28, 19, 4995, 5006, May 2008, [Peer-reviewed]
English, Scientific journal - Role of the internal Shank-binding segment of glutamate receptor delta 2 in synaptic localization and cerebellar functions
Misato Yasumura, Takeshi Uemura, Miwako Yamasaki, Kenji Sakimura, Masahiko Watanabe, Masayoshi Mishina
NEUROSCIENCE LETTERS, 433, 2, 146, 151, Mar. 2008, [Peer-reviewed]
English, Scientific journal - ERK is required for developmental synapse elimination in the cerebellum
Harada Takeshi, Hirai Yoshie, Yamasaki Miwako, Hashimoto Kouichi, Nakao Harumi, Tabata Toshihide, Watanabe Masahiko, Kano Masanobu, Aiba Atsu
Neuroscience Research, 61, S57, 2008, [Peer-reviewed]
International conference proceedings - The C-terminal domain of GluR delta 2 is essential for cerebellar LTD and regulation of climbing fiber territory at parallel fiber synapses in cerebellar Purkinje cells
Uemura Takeshi, Kakizavva Sho, Yamasaki Miwako, Sakimura Kenji, Watanabe Masahiko, Iino Masamitsu, Mishina Masayoshi
JOURNAL OF PHARMACOLOGICAL SCIENCES, 106, 80P, 2008, [Peer-reviewed] - P3-c2O Role of the internal Shank-binding segment of GluR delta 2 in cerebellar functions
Yasumura Misato, Uemura Takeshi, Yamasaki Miwako, Sakimura Kenji, Watanabe Masahiko, Mishina Masayoshi
NEUROSCIENCE RESEARCH, 61, S221, 2008, [Peer-reviewed] - Hole of the C-terminal PDZ binding domain of glutamate receptor delta 2 in synaptic plasticity and climbing fiber wiring
Uemura Takeshi, Kakizawa Sho, Yamasaki Miwako, Sakimura Kenji, Watanabe Masahiko, Lino Masamitsu, Mishina Masayoshi
NEUROSCIENCE RESEARCH, 61, S219, 2008, [Peer-reviewed] - Roles of the internal PDZ-binding domain of GluR delta 2 in synaptic localization and cerebellar functions
Yasumura Misato, Uemura Takeshi, Yamasaki Miwako, Sakimura Kenji, Watanabe Masahiko, Mishina Masayoshi
JOURNAL OF PHARMACOLOGICAL SCIENCES, 106, 133P, 2008, [Peer-reviewed] - Regulation of long-term depression and climbing fiber territory by glutamate receptor delta 2 at parallel fiber synapses through its c-terminal domain in cerebellar Purkinje cells
Takeshi Uemura, Sho Kakizawa, Miwako Yamasaki, Kenji Sakimura, Masahiko Watanabe, Masamitsu Iino, Masayoshi Mishina
JOURNAL OF NEUROSCIENCE, 27, 44, 12096, 12108, Oct. 2007, [Peer-reviewed]
English, Scientific journal - Miniature synaptic events elicited by presynaptic Ca2+ rise are selectively suppressed by cannabinoid receptor activation in cerebellar Purkinje cells
M Yamasaki, K Hashimoto, M Kano
JOURNAL OF NEUROSCIENCE, 26, 1, 86, 95, Jan. 2006, [Peer-reviewed], [Lead author]
English, Scientific journal - 3-Phosphoglycerate dehydrogenase, a key enzyme for L-serine biosynthesis, is preferentially expressed in the radial glia/astrocyte lineage and olfactory ensheathing glia in the mouse brain
Miwako Yamasaki, Keiko Yamada, Shigeki Furuya, Junya Mitoma, Yoshio Hirabayashi, Masahiko Watanabe
Journal of Neuroscience, 21, 19, 7691, 7704, 19, 01 Oct. 2001, [Peer-reviewed], [Lead author]
English - L-Serine and glycine serve as major astroglia-derived trophic factors for cerebellar Purkinje neurons
Shigeki Furuya, Toshihide Tabata, Junya Mitoma, Keiko Yamada, Miwako Yamasaki, Asami Makino, Toshifumi Yamamoto, Masahiko Watanabe, Masanobu Kano, Yoshio Hirabayashi
Proceedings of the National Academy of Sciences of the United States of America, 97, 21, 11528, 11533, 21, 10 Oct. 2000, [Peer-reviewed]
Scientific journal - Critical period for activity-dependent synapse elimination in developing cerebellum
S Kakizawa, M Yamasaki, M Watanabe, M Kano
JOURNAL OF NEUROSCIENCE, 20, 13, 4954, 4961, Jul. 2000, [Peer-reviewed]
English, Scientific journal - Gq protein alpha subunits G alpha q and G alpha 11 are localized at postsynaptic extra-junctional membrane of cerebellar Purkinje cells and hippocampal pyramidal cells
J Tanaka, S Nakagawa, E Kushiya, M Yamasaki, M Fukaya, T Iwanaga, MI Simon, K Sakimura, M Kano, M Watanabe
EUROPEAN JOURNAL OF NEUROSCIENCE, 12, 3, 781, 792, Mar. 2000, [Peer-reviewed]
English, Scientific journal
Other Activities and Achievements
- Olig2アストロサイトの脳内分布と抑制性シナプスとの関与
辰巳晃子, 石西綾美, 山崎美和子, 河邉良枝, 森田(竹村)晶子, 中原一貴, 奥田洋明, 田中達英, 和中明生, 日本解剖学会総会・全国学術集会講演プログラム・抄録集, 124th, 2019 - Unique neural characteristics of GAD67-containing 5-HTergic neurons in the rat dorsal raphe nucleus
Shikanai Hiroki, Yoshida Takayuki, Konno Kohtarou, Yamasaki Miwako, Izumi Takeshi, Ohmura Yu, Shimamura Keiichi, Watanabe Masahiko, Yoshioka Mitsuhiro, JOURNAL OF PHARMACOLOGICAL SCIENCES, 121, 65P, 2013, [Peer-reviewed] - Distinct neurochemical and functional properties of GAD67-containing 5-HT neurons in the rat dorsal raphe nucleus
鹿内 浩樹, 吉田 隆行, 今野 幸太郎, 山崎 美和子, 泉 剛, 大村 優, 渡邊 雅彦, 吉岡 充弘, 北海道醫學雜誌 = Acta medica Hokkaidonensia, 87, 6, 288, 288, 01 Nov. 2012
Japanese - Lack of Molecular-Anatomical Evidence for GABAergic Influence on Axon Initial Segment of Cerebellar Purkinje Cells by the Pinceau Formation
岩倉 淳, 内ヶ島 基政, 宮崎 大輔, 山崎 美和子, 渡辺 雅彦, 北海道醫學雜誌 = Acta medica Hokkaidonensia, 87, 6, 273, 273, 01 Nov. 2012
Japanese - Developmental switching of perisomatic innervation from climbing fibers to basket cell fibers in cerebellar Purkinje cells
市川 量一, 山崎 美和子, 宮崎 太輔, 今野 幸太郎, 橋本 浩一, 辰巳 治之, 井上 芳郎, 狩野 正伸, 渡辺 雅彦, 北海道醫學雜誌 = Acta medica Hokkaidonensia, 87, 2, 73, 73, 01 Apr. 2012
Japanese - Unique inhibitory synapse with particularly rich endocannabinoid signaling machinery on pyramidal neurons in basal amygdaloid nucleus
吉田 隆行, 内ヶ島 基政, 山崎 美和子, イストバンカトナ, 山崎 真弥, 崎村 建司, 狩野 方伸, 吉岡 充弘, 渡辺 雅彦, 北海道醫學雜誌 = Acta medica Hokkaidonensia, 87, 2, 72, 72, 01 Apr. 2012
Japanese - シナプス外グルタミン酸動態の可視化解析
大久保洋平, 関谷敬, 並木繁行, 坂本寛和, 坂本寛和, 飯沼将, 山崎美和子, 渡辺雅彦, 廣瀬謙造, 飯野正光, 日本薬理学会関東部会プログラム・要旨集, 120th, 2009
Research Themes
- Developmental neural circuit formation based on the competition between excitatory and inhibitory inputs in the cerebellum
Grants-in-Aid for Scientific Research
01 Apr. 2022 - 31 Mar. 2025
宮崎 太輔, 山崎 美和子
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 22K06784 - 発達期からの慢性ニコチン曝露がもたらす神経回路変容の統合的理解
科学研究費助成事業 基盤研究(B)
01 Apr. 2020 - 31 Mar. 2024
山崎 美和子, 宮崎 太輔
ニコチン性アセチルコリン受容体(nAChR)は、タバコの主成分であるニコチンと結合することにより様々な神経伝達修飾作用を及ぼす。よく知られたニコチン依存に加え、近年では発達期からのニコチン曝露がオピオイド系を始めとする薬物依存への道筋をつけるという新たな可能性が示唆されているが、その生物学的なメカニズムや脳内でnAChRの局在やその分子機構にも未だ不明な点が多い。本研究ではnAChRを介した神経伝達修飾の解剖学的な基盤を示し、発達期からのニコチン曝露が神経回路にどのような構造的・機能的な変容をもたらすかを明らかにする。今年度は以下の二項目で進捗があった。
1)a7サブユニットに対する特異抗体の開発:脳内の主要サブユニットであるa7サブユニットに関し、生化学解析に使用できる抗体は既に開発していたが、今年度、脳組織での免疫染色に使用可能な特異抗体の開発に成功した。野生型マウスでは、陽性シグナルが大脳皮質第１層や海馬の上昇層の抑制性介在ニューロンや、赤核、二丘体傍核に存在していた。これに対し、a7欠損マウスではシグナルが検出されず、特異性が確認された。また、a7サブユニットのアセンブリに必要なシャペロンTMEM35欠損マウスでもシグナルが検出されなかった。このことはa7の細胞膜への輸送ではなく、アセンブリにTMEM35Aが必須であることを示唆している。また、組織染色に有用というだけでなく、生化学解析での感度・特異度ともに高く今後の解析に非常に有用なツールとして期待できる。
2) b4サブニットに対する特異抗体の開発:b4サブニットに対する特異抗体の開発に成功した。内側手綱核-脚間核投射系に選択的に局在していることが確認された。
日本学術振興会, 基盤研究(B), 北海道大学, 20H03410 - 認知・運動における多領野間脳情報動態の光学的計測と制御
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
Sep. 2017 - Mar. 2022
Kazuo Kitamura
MEXT, Competitive research funding - Elucidating the mechanisms underlying selective NR3A accumulation at non-synaptic junctions
Fund for the Promotion of Joint International Research (Fostering Joint International Research)
Jan. 2018 - Mar. 2021
Miwako Yamasaki
In the preceding project, we found that NR3A selectively localized to non-synaptic contacts between climbing fiber and cerebellar stellate cells, and those between glutamatergic terminals and somatostatin-positive GABAergic interneurons in the cerebral cortex. To identify molecular partners that constitute biochemical complex, we immunopurified biochemical complex containing NR3A and conducted analysis by mass spectrometry. We found that NR1 but not Kv4.3 was included in the complex. Furthermore, in a reconstitution system using Xenopus oocytes, NR3A assembly required NR1, but not Kv4.3. Rescue experiment using AAV revealed that NR1 was required for selective NR3A expression at non-synaptic contacts.
MEXT, Fund for the Promotion of Joint International Research (Fostering Joint International Research), Hokkaido University, Principal investigator, Competitive research funding, 17KK0160 - 経路選択的な標識・操作技術を応用したマーモセット大脳皮質―基底核 ネットワークの構造・機能マッピング
Brain/Minds
Apr. 2017 - Mar. 2021
Kazuto Kobayashi
AMED, Competitive research funding - 非シナプス性結合に入力経路・細胞選択的に集積するNR3A受容体の機能的意義の解明
Grant-in-Aid for Scientific Research (C)
Apr. 2017 - Mar. 2020
Miwako Yamasaki
MEXT, Principal investigator, Competitive research funding - Analysis for heterosynaptic competition between parallel and climbing fiber in mature Purkinje cells
Grants-in-Aid for Scientific Research
01 Apr. 2014 - 31 Mar. 2017
Miyazaki Taisuke, YAMASAKI MIWAKO
Purkinje cells receive two excitatory inputs, parallel fiber (PF) and climbing fiber (CF). This PC circuitry is established by heterosynaptic competition between PF and CF, fueled by glutamate receptor GluRδ2 and voltage-gated calcium ion channel Cav2.1, respectively. However, it has been unclear whether this heterosynaptic competition maintains PC circuitry in the adult cerebellum. To uncover this question, I investigated novel mouse line, in which Cav2.1 gene can be deleted in adult PCs by the drug-induced ablation system. In anatomical and electrophysiological investigation, inducible Cav2.1 ablation in the adult cerebellum caused motor discoordination and imbalance of heterosynaptic competiton with proximal expansion of PF territory. Therefore, Cav2.1 fuels CF inputs and balance heterosynaptic competition in the adult cerebellum. This result strongly suggests that the balance of heterosynaptic competition is essential for the cerebellar function.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 26460250 - Molecular-anatomical research on multi-modal regulation of synaptic transmission in higher brain regions
Grants-in-Aid for Scientific Research
31 May 2012 - 31 Mar. 2017
WATANABE MASAHIKO, Yamasaki Miwako, Miyazaki Taisuke, Konno Kohtarou, Uchigashima Motokazu, Kano Masanobu, Shigemoto Ryuichi, Kobayashi Kazuto
state-dependent manners. We found that TARP and GluD families play important roles in input-, target cell-, activity-dependent regulations in the cerebellum and hippocampus. In the cortex and cortex-like amygdala, CCK-positive interneurons expressing VGluT3 constructed unique invaginating synapses, which were also characterized by intense expression of endocannabinoid signaling molecules to powerfully drive activity- and state-dependent disinhibition. Furthermore, so-called ‘dopamine synapses’ are important for state-dependent controls of motor and cognitive functions. We address that dopamine synapses were neuroligin-2-mediated heterologous contacts formed between dopaminergic presynapse and GABAergic postsynapse, from which we propose the third mode of neural transmission, anchored transmission, in addition to classical modes of wired and volume transmissions.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (S), Hokkaido University, 24220007 - 成体マウス脳で非シナプス結合に選択的に発現するNR3A受容体の機能的意義
Research Grant from Takeda Science Foundation
Apr. 2016 - Mar. 2017
Miwako Yamasaki
Takeda Science Foundation, Principal investigator, Competitive research funding - 海馬におけるアセチルコリン作動性神経依存的な記憶形成機構の分子解剖学的基盤
Grant-in-Aid for Female Researchers
Apr. 2014 - Mar. 2016
Miwako Yamasaki
The Naito Foundation, Principal investigator, Competitive research funding - バレル神経回路の機能発達におけるニコチン性アセチルコリン受容体の役割
Grant-in-Aid for Scientific Research (C)
Apr. 2014 - Mar. 2016
Miwako Yamasaki
MEXT, Principal investigator, Competitive research funding - ＮＭＤＡ受容体を介する興奮・抑制バランス依存的なバレル神経回路形成制御機構
Grant-in-Aid for Young Scientists (B)
Apr. 2012 - Mar. 2014
Miwako Yamasaki
MEXT, Principal investigator, Competitive research funding - Molecular mechanisms for calcium-mediated refinement of competitive synaptic wiring in the brain
Grants-in-Aid for Scientific Research
2007 - 2011
WATANABE Masahiko, SAKIMURA Kenji, KANO Masanobu, AIBA Atsu, FUKAYA Masahiro, YAMASAKI Miwako, MIYAZAKI Taisuke, KANO Masanobu, AIBA Atsu, FUKAYA Masahiro, YAMASAKI Miwako, MIYAZAKI Taisuke
Synaptic circuits in neonates are characterized by excess, overlapping and entangled wiring. These immature circuits are refined into functional and mature ones through use-dependent and activity-dependent strengthening and weakening/elimination of immature synapses. Through this process, almost all of higher brain functions develop robustly during sensitive or critical period of early postnatal life, including cognition, language, music performance, sports, intelligence, thought, personality, and sociality in the case of human beings. Now we understand that the activity dependent synaptic circuit development is facilitated by glutamate receptor activation and subsequent calcium influx into postsynaptic neurons. However little is known about how calcium influx regulates competitive synaptic development. In this research project, we aimed to clarify this issue by focusing on calcium-dependent and-independent mechanisms using neuroanatomical, electrophysiological, and developmental biological technologies. Through this research project, I clarified that P/Q-type calcium channels promote the development and maturation of climbing fiber innervation to Purkinje cells in the cerebellum, while calcium-permeable glutamate receptors and transporters regulate synaptic circuit development in the somatosensory cortex. Moreover, the GluD2-Cbln1-neurexin system controls the connectivity of parallel fiber-Purkinje cell synapses to compete with climbing fiber innervation promoted by P/Q-type calcium channels.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (S), Hokkaido University, 19100005 - １次抗体直接標識プローブの開発と実用性に関する検討
seeds
Apr. 2009 - Mar. 2010
Miwako Yamasaki
JST, Principal investigator, Competitive research funding - 余剰登上線維除去に先行して起こるmGluR1依存的な登上線維シナプス強化過程
Grant-in-Aid for Young Scientists (B)
Apr. 2007 - Mar. 2009
Miwako Yamasaki
MEXT, Principal investigator, Competitive research funding - 活動依存的に誘導されるGPIアンカー蛋白質の小脳内分布とシナプス機能発達との関連
Grant-in-Aid for JSPS Fellows
Apr. 2003 - Mar. 2006
Miwako Yamasaki
JSPS, Principal investigator, Competitive research funding
