Miyazaki Taisuke
| Faculty of Health Sciences Health Sciences Department of Rehabilitation Science | Associate Professor |
Last Updated :2026/04/14
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- Bachelor's degree program, Departments of Health Sciences, School of Medicine
- Master's degree program, Graduate School of Health Sciences
- Doctoral (PhD) degree program, Graduate School of Health Sciences
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Career
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Awards
- Sep. 2020, 日本解剖学会 東北・北海道連合支部会, 学会賞
小脳抑制性介在ニューロンルガロ細胞の帯状構造特異的な入出力様式
宮﨑太輔,山崎美和子、田中謙二, 渡辺雅彦 - 2017, 北海道大学, 北海道大学医学部 優秀論文賞
Glutamate transporter GLAST controls synaptic wrapping by Bergmann glia and ensures proper wiring of Purkinje cells
宮崎太輔 - 2009, 日本解剖学会, 解剖学会奨励賞
異種および同種入力線維間の競合を基盤とする小脳シナプス回路発達の分子機構に関する神経解剖学的研究
宮崎太輔
Papers
- mGluR1 signaling is necessary for strengthening winner climbing fiber inputs in the developing mouse cerebellum
Miwako Yamasaki, Taisuke Miyazaki, Kouichi Hashimoto, Norio Takei, Atsu Aiba, Masanobu Kano, Masahiko Watanabe
Proceedings of the National Academy of Sciences, 123, 4, Proceedings of the National Academy of Sciences, 23 Jan. 2026
Scientific journal, Functional neural circuits are sculpted by strengthening frequently used synapses and removing unnecessary connections. At birth, cerebellar Purkinje cells receive inputs with similar synaptic strengths from multiple climbing fibers (CFs). During postnatal development, a single “winner” CF is selectively strengthened and expands its dendritic innervation territory, while somatic “loser” synapses are eliminated. Here, we report that deleting metabotropic glutamate receptor 1 (mGluR1) or protein kinase Cγ (PKCγ) in mice disrupts this selective strengthening and territory expansion of “winner” CFs during early development. This impairment leads to weaker synaptic transmission and diminished dendritic innervation territory of “winner” CFs at later stages. Notably, “winner” CF synapses in these mutants exhibit impaired long-term potentiation, reduced AMPA receptor expression, and simpler postsynaptic organizations. These findings reveal a previously unappreciated role for mGluR1–PKCγ signaling, besides its established role in eliminating “loser” CFs, in promoting the functional and structural maturation of “winner” CF synapses. - The ER/Golgi Protein FNDC3B Facilitates Climbing Fibre to Purkinje Cell Synapse Elimination in the Developing Mouse Cerebellum.
Céline Louise Mercier, Takaki Watanabe, Yuto Okuno, Kyoko Matsuyama, Kyoko Kushibe, Henry Denny, Taisuke Miyazaki, Miwako Yamasaki, Meiko Kawamura, Manabu Abe, Kenji Sakimura, Masahiko Watanabe, Naofumi Uesaka, Masanobu Kano
The European journal of neuroscience, 63, 2, e70411, Jan. 2026, [International Magazine]
English, Scientific journal, Synapse elimination during development is crucial for refining neural circuits by removing excess synapses formed around birth. In the neonatal cerebellum, Purkinje cells (PCs) are initially innervated by multiple climbing fibers (CFs) with similar synaptic strengths. During subsequent postnatal development, a single CF is strengthened and retained, while the other CFs are eliminated. Here, our PC-specific RNAi knockdown (KD) screening revealed that fibronectin type III domain containing 3B (FNDC3B), an endoplasmic reticulum protein, was involved in CF synapse elimination from around postnatal day 9 (P9) in mice. We showed that FNDC3B mRNA was expressed in PCs during CF synapse elimination. In PC-selective FNDC3B conditional knockout (FNDC3B-cKO) mice, CF synapse elimination from P10 was impaired, and the extension of CFs along PC dendrites was reduced at P21. However, these phenotypes were recovered by P40. In contrast, parallel fiber-mediated excitatory synaptic inputs and inhibitory synaptic inputs to PCs were not affected in FNDC3B-cKO mice. These results suggest that FNDC3B facilitates CF synapse elimination during postnatal development, highlighting a new role of FNDC3B in the developing brain. - The transcription factor ZFP64 promotes activity-dependent synapse elimination during postnatal cerebellar development.
Jianling Zhang, Takaki Watanabe, Taisuke Miyazaki, Miwako Yamasaki, Kohtarou Konno, Yuto Okuno, Kyoko Matsuyama, Takayuki Noro, Masahiko Watanabe, Naofumi Uesaka, Masanobu Kano
iScience, 28, 6, 112746, 112746, 20 Jun. 2025, [International Magazine]
English, Scientific journal, Eliminating redundant synapses formed around birth is essential for shaping functionally mature neural circuits during postnatal development. Each Purkinje cell (PC) in the neonatal mouse cerebellum receives synaptic inputs from multiple climbing fibers (CFs). Only one CF is strengthened and extends its innervation over PC dendrites, whereas the other CFs are eventually pruned during postnatal development. These events are believed to require proper gene expression, but the underlying mechanisms are not yet understood. Here, we report that the transcription factor ZFP64 in PCs mediates part of CF synapse elimination events presumably downstream of P/Q-type voltage-dependent Ca2+ channels (P/Q-VDCCs). PC-specific knockdown (KD) of ZFP64 during postnatal development delayed the elimination of redundant CF synapses and the dendritic extension of CF innervation. The KD of semaphorin 3A (Sema3A) in PCs partially restored the effects of ZFP64 or P/Q-VDCC KD. We propose that ZFP64 promotes developmental CF synapse elimination by regulating Sema3A expression. - 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, [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, [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. - Reduced GABAergic inhibition and impaired synapse elimination by neuroligin-2 deletion from Purkinje cells of the developing cerebellum.
Esther Suk King Lai, Naofumi Uesaka, Taisuke Miyazaki, Kouichi Hashimoto, Masahiko Watanabe, Masanobu Kano
Frontiers in neural circuits, 19, 1530141, 1530141, 2025, [International Magazine]
English, Scientific journal, Functionally mature neural circuits are shaped during postnatal development by eliminating redundant synapses formed around birth. This process is known as synapse elimination and requires a proper balance of excitation and inhibition. Neuroligin-2 (NL2) is a postsynaptic cell adhesion molecule required for the formation, maintenance, and function of inhibitory synapses. However, how NL2 regulates synapse elimination during postnatal development is largely unknown. Here we report that the deletion of NL2 from Purkinje cells (PCs) in the cerebellum impairs the developmental elimination of redundant climbing fiber (CF) to PC synapses. In global NL2-knockout (KO) mice, GABAergic inhibition to PCs was attenuated and CF synapse elimination was impaired after postnatal day 10 (P10). These phenotypes were restored by the expression of NL2 into PCs of NL2-KO mice. Moreover, microRNA-mediated knockdown of NL2 specifically from PCs during development caused attenuated inhibition and impaired CF synapse elimination. In PCs innervated by "strong" and "weak" CFs, calcium transients elicited by "weak" CFs were enhanced in NL2-deficient PCs, suggesting that excess calcium signaling permits the survival of redundant "weak" CF synapses. We conclude that NL2 is crucial for maintaining inhibitory synaptic function and properly eliminating redundant CF synapses during postnatal development. - Direct and indirect pathways for heterosynaptic interaction underlying developmental synapse elimination in the mouse cerebellum.
Hisako Nakayama, Taisuke Miyazaki, Manabu Abe, Maya Yamazaki, Yoshinobu Kawamura, Myeongjeong Choo, Kohtarou Konno, Shinya Kawata, Naofumi Uesaka, Kouichi Hashimoto, Mariko Miyata, Kenji Sakimura, Masahiko Watanabe, Masanobu Kano
Communications biology, 7, 1, 806, 806, 03 Jul. 2024, [International Magazine]
English, Scientific journal, Developmental synapse elimination is crucial for shaping mature neural circuits. In the neonatal mouse cerebellum, Purkinje cells (PCs) receive excitatory synaptic inputs from multiple climbing fibers (CFs) and synapses from all but one CF are eliminated by around postnatal day 20. Heterosynaptic interaction between CFs and parallel fibers (PFs), the axons of cerebellar granule cells (GCs) forming excitatory synapses onto PCs and molecular layer interneurons (MLIs), is crucial for CF synapse elimination. However, mechanisms for this heterosynaptic interaction are largely unknown. Here we show that deletion of AMPA-type glutamate receptor functions in GCs impairs CF synapse elimination mediated by metabotropic glutamate receptor 1 (mGlu1) signaling in PCs. Furthermore, CF synapse elimination is impaired by deleting NMDA-type glutamate receptors from MLIs. We propose that PF activity is crucial for CF synapse elimination by directly activating mGlu1 in PCs and indirectly enhancing the inhibition of PCs through activating NMDA receptors in MLIs. - 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, [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. - Neuronal DSCAM regulates the peri-synaptic localization of GLAST in Bergmann glia for functional synapse formation
Ken-ichi Dewa, Nariko Arimura, Wataru Kakegawa, Masayuki Itoh, Toma Adachi, Satoshi Miyashita, Yukiko U. Inoue, Kento Hizawa, Kei Hori, Natsumi Honjoya, Haruya Yagishita, Shinichiro Taya, Taisuke Miyazaki, Chika Usui, Shoji Tatsumoto, Akiko Tsuzuki, Hirotomo Uetake, Kazuhisa Sakai, Kazuhiro Yamakawa, Takuya Sasaki, Jun Nagai, Yoshiya Kawaguchi, Masaki Sone, Takayoshi Inoue, Yasuhiro Go, Noritaka Ichinohe, Kozo Kaibuchi, Masahiko Watanabe, Schuichi Koizumi, Michisuke Yuzaki, Mikio Hoshino
Nature Communications, 15, 1, Springer Science and Business Media LLC, 01 Feb. 2024
Scientific journal, Abstract
In the central nervous system, astrocytes enable appropriate synapse function through glutamate clearance from the synaptic cleft; however, it remains unclear how astrocytic glutamate transporters function at peri-synaptic contact. Here, we report that Down syndrome cell adhesion molecule (DSCAM) in Purkinje cells controls synapse formation and function in the developing cerebellum. Dscam-mutant mice show defects in CF synapse translocation as is observed in loss of function mutations in the astrocytic glutamate transporter GLAST expressed in Bergmann glia. These mice show impaired glutamate clearance and the delocalization of GLAST away from the cleft of parallel fibre (PF) synapse. GLAST complexes with the extracellular domain of DSCAM. Riluzole, as an activator of GLAST-mediated uptake, rescues the proximal impairment in CF synapse formation in Purkinje cell-selective Dscam-deficient mice. DSCAM is required for motor learning, but not gross motor coordination. In conclusion, the intercellular association of synaptic and astrocyte proteins is important for synapse formation and function in neural transmission. - 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, [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. - Excitatory and inhibitory receptors utilize distinct post- and trans-synaptic mechanisms in vivo.
Taisuke Miyazaki, Megumi Morimoto-Tomita, Coralie Berthoux, Kotaro Konno, Yoav Noam, Tokiwa Yamasaki, Matthijs Verhage, Pablo E Castillo, Masahiko Watanabe, Susumu Tomita
eLife, 10, 18 Oct. 2021, [International Magazine]
English, Scientific journal, Ionotropic neurotransmitter receptors at postsynapses mediate fast synaptic transmission upon binding of the neurotransmitter. Post- and trans-synaptic mechanisms through cytosolic, membrane, and secreted proteins have been proposed to localize neurotransmitter receptors at postsynapses. However, it remains unknown which mechanism is crucial to maintain neurotransmitter receptors at postsynapses. In this study, we ablated excitatory or inhibitory neurons in adult mouse brains in a cell-autonomous manner. Unexpectedly, we found that excitatory AMPA receptors remain at the postsynaptic density upon ablation of excitatory presynaptic terminals. In contrast, inhibitory GABAA receptors required inhibitory presynaptic terminals for their postsynaptic localization. Consistent with this finding, ectopic expression at excitatory presynapses of neurexin-3 alpha, a putative trans-synaptic interactor with the native GABAA receptor complex, could recruit GABAA receptors to contacted postsynaptic sites. These results establish distinct mechanisms for the maintenance of excitatory and inhibitory postsynaptic receptors in the mature mammalian brain. - An Autism-Associated Neuroligin-3 Mutation Affects Developmental Synapse Elimination in the Cerebellum.
Esther Suk King Lai, Hisako Nakayama, Taisuke Miyazaki, Takanobu Nakazawa, Katsuhiko Tabuchi, Kouichi Hashimoto, Masahiko Watanabe, Masanobu Kano
Frontiers in neural circuits, 15, 676891, 676891, 2021, [International Magazine]
English, Scientific journal, Neuroligin is a postsynaptic cell-adhesion molecule that is involved in synapse formation and maturation by interacting with presynaptic neurexin. Mutations in neuroligin genes, including the arginine to cystein substitution at the 451st amino acid residue (R451C) of neuroligin-3 (NLGN3), have been identified in patients with autism spectrum disorder (ASD). Functional magnetic resonance imaging and examination of post-mortem brain in ASD patients implicate alteration of cerebellar morphology and Purkinje cell (PC) loss. In the present study, we examined possible association between the R451C mutation in NLGN3 and synaptic development and function in the mouse cerebellum. In NLGN3-R451C mutant mice, the expression of NLGN3 protein in the cerebellum was reduced to about 10% of the level of wild-type mice. Elimination of redundant climbing fiber (CF) to PC synapses was impaired from postnatal day 10-15 (P10-15) in NLGN3-R451C mutant mice, but majority of PCs became mono-innervated as in wild-type mice after P16. In NLGN3-R451C mutant mice, selective strengthening of a single CF relative to the other CFs in each PC was impaired from P16, which persisted into juvenile stage. Furthermore, the inhibition to excitation (I/E) balance of synaptic inputs to PCs was elevated, and calcium transients in the soma induced by strong and weak CF inputs were reduced in NLGN3-R451C mutant mice. These results suggest that a single point mutation in NLGN3 significantly influences the synapse development and refinement in cerebellar circuitry, which might be related to the pathogenesis of ASD. - TMEM163 Regulates ATP-Gated P2X Receptor and Behavior.
Salm EJ, Dunn PJ, Shan L, Yamasaki M, Malewicz NM, Miyazaki T, Park J, Sumioka A, Hamer RRL, He WW, Morimoto-Tomita M, LaMotte RH, Tomita S
Cell Rep., 31, 2, 107704, 107704, Jun. 2020, [Peer-reviewed], [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. - Compartmentalized input-output organization of Lugaro cells in the cerebellar cortex.
Miyazaki T, Yamasaki M, Tanaka KF, Watanabe M
Neuroscience., 10, 462, 89, 105, May 2020, [Peer-reviewed], [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. - 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. - Elavl3 is essential for the maintenance of Purkinje neuron axons.
Ogawa Y, Kakumoto K, Yoshida T, Kuwako KI, Miyazaki T, Yamaguchi J, Konno A, Hata J, Uchiyama Y, Hirai H, Watanabe M, Darnell RB, Okano H, Okano HJ
Scientific reports, 8, 1, 2722, 2722, Feb. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, Neuronal Elav-like (nElavl or neuronal Hu) proteins are RNA-binding proteins that regulate RNA stability and alternative splicing, which are associated with axonal and synaptic structures. nElavl proteins promote the differentiation and maturation of neurons via their regulation of RNA. The functions of nElavl in mature neurons are not fully understood, although Elavl3 is highly expressed in the adult brain. Furthermore, possible associations between nElavl genes and several neurodegenerative diseases have been reported. We investigated the relationship between nElavl functions and neuronal degeneration using Elavl3-/- mice. Elavl3-/- mice exhibited slowly progressive motor deficits leading to severe cerebellar ataxia, and axons of Elavl3-/- Purkinje cells were swollen (spheroid formation), followed by the disruption of synaptic formation of axonal terminals. Deficit in axonal transport and abnormalities in neuronal polarity was observed in Elavl3-/- Purkinje cells. These results suggest that nElavl proteins are crucial for the maintenance of axonal homeostasis in mature neurons. Moreover, Elavl3-/- mice are unique animal models that constantly develop slowly progressive axonal degeneration. Therefore, studies of Elavl3-/- mice will provide new insight regarding axonal degenerative processes. - Maturation of Cerebellar Purkinje Cell Population Activity during Postnatal Refinement of Climbing Fiber Network
Jean-Marc Good, Michael Mahoney, Taisuke Miyazaki, Kenji F. Tanaka, Kenji Sakimura, Masahiko Watanabe, Kazuo Kitamura, Masanobu Kano
CELL REPORTS, 21, 8, 2066, 2073, Nov. 2017, [Peer-reviewed]
English, Scientific journal - Alternative splicing in the C-terminal tail of Ca(v)2.1 is essential for preventing a neurological disease in mice
Tomonori Aikawa, Takaki Watanabe, Taisuke Miyazaki, Takayasu Mikuni, Minoru Wakamori, Miyano Sakurai, Hidenori Aizawa, Nobutaka Ishizu, Masahiko Watanabe, Masanobu Kano, Hidehiro Mizusawa, Kei Watase
HUMAN MOLECULAR GENETICS, 26, 16, 3094, 3104, Aug. 2017, [Peer-reviewed]
English, Scientific journal - Retrograde BDNF to TrkB signaling promotes synapse elimination in the developing cerebellum
Myeongjeong Choo, Taisuke Miyazaki, Maya Yamazaki, Meiko Kawamura, Takanobu Nakazawa, Jianling Zhang, Asami Tanimura, Naofumi Uesaka, Masahiko Watanabe, Kenji Sakimura, Masanobu Kano
NATURE COMMUNICATIONS, 8, 1, 195, 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 - Serotonin rebalances cortical tuning and behavior linked to autism symptoms in 15q11-13 CNV mice
Nobuhiro Nakai, Masatoshi Nagano, Fumihito Saitow, Yasuhito Watanabe, Yoshinobu Kawamura, Akiko Kawamoto, Kota Tamada, Hiroshi Mizuma, Hirotaka Onoe, Yasuyoshi Watanabe, Hiromu Monai, Hajime Hirase, Jin Nakatani, Hirofumi Inagaki, Tomoyuki Kawada, Taisuke Miyazaki, Masahiko Watanabe, Yuka Sato, Shigeo Okabe, Kazuo Kitamura, Masanobu Kano, Kouichi Hashimoto, Hidenori Suzuki, Toru Takumi
SCIENCE ADVANCES, 3, 6, e1603001, Jun. 2017, [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 - 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 - Medial septal GABAergic projection neurons promote object exploration behavior and type 2 theta rhythm
Gireesh Gangadharan, Jonghan Shin, Seong-Wook Kim, Angela Kim, Afshin Paydar, Duk-Soo Kim, Taisuke Miyazaki, Masahiko Watanabe, Yuchio Yanagawa, Jinhyun Kim, Yeon-Soo Kim, Daesoo Kim, Hee-Sup Shin
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 113, 23, 6550, 6555, Jun. 2016, [Peer-reviewed]
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 - 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 - Combined immunocytochemistry and tracing of neural connections
Taisuke Miyazaki, Masahiko Watanabe
Immunocytochemistry and Related Techniques, 299, 311, Springer New York, 24 Feb. 2015, [Peer-reviewed]
English, In book - Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism
Claire Piochon, Alexander D. Kloth, Giorgio Grasselli, Heather K. Titley, Hisako Nakayama, Kouichi Hashimoto, Vivian Wan, Dana H. Simmons, Tahra Eissa, Jin Nakatani, Adriana Cherskov, Taisuke Miyazaki, Masahiko Watanabe, Toru Takumi, Masanobu Kano, Samuel S. -H. Wang, Christian Hansel
NATURE COMMUNICATIONS, 6, 6014, Jan. 2015, [Peer-reviewed]
English - Chemical corrector treatment ameliorates increased seizure susceptibility in a mouse model of familial epilepsy
Norihiko Yokoi, Yuko Fukata, Daisuke Kase, Taisuke Miyazaki, Martine Jaegle, Toshika Ohkawa, Naoki Takahashi, Hiroko Iwanari, Yasuhiro Mochizuki, Takao Hamakubo, Keiji Imoto, Dies Meijer, Masahiko Watanabe, Masaki Fukata
NATURE MEDICINE, 21, 1, 19, 26, Jan. 2015, [Peer-reviewed]
English, Scientific journal - Structure-Function Relationships between Aldolase C/Zebrin II Expression and Complex Spike Synchrony in the Cerebellum
Shinichiro Tsutsumi, Maya Yamazaki, Taisuke Miyazaki, Masahiko Watanabe, Kenji Sakimura, Masanobu Kano, Kazuo Kitamura
JOURNAL OF NEUROSCIENCE, 35, 2, 843, 852, Jan. 2015, [Peer-reviewed]
English, Scientific journal - Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism
Claire Piochon, Alexander D. Kloth, Giorgio Grasselli, Heather K. Titley, Hisako Nakayama, Kouichi Hashimoto, Vivian Wan, Dana H. Simmons, Tahra Eissa, Jin Nakatani, Adriana Cherskov, Taisuke Miyazaki, Masahiko Watanabe, Toru Takumi, Masanobu Kano, Samuel S. -H. Wang, Christian Hansel
NATURE COMMUNICATIONS, 5, 5586, Nov. 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 - A New Mouse Allele of Glutamate Receptor Delta 2 with Cerebellar Atrophy and Progressive Ataxia
Yuka Miyoshi, Yoshichika Yoshioka, Kinuko Suzuki, Taisuke Miyazaki, Minako Koura, Kazumasa Saigoh, Naoko Kajimura, Yoko Monobe, Susumu Kusunoki, Junichiro Matsuda, Masahiko Watanabe, Naoto Hayasaka
PLOS ONE, 9, 9, e107867, 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 - 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 - Disruption of cerebellar microzonal organization in GluD2 (GluR delta 2) knockout mouse
Miki Hashizume, Taisuke Miyazaki, Kenji Sakimura, Masahiko Watanabe, Kazuo Kitamura, Masanobu Kano
FRONTIERS IN NEURAL CIRCUITS, 7, 130, Aug. 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, 46, 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.
Kudo T, Uchigashima M, Miyazaki T, Konno K, Yamasaki M, Yanagawa Y, Minami M, Watanabe M
The Journal of neuroscience : the official journal of the Society for Neuroscience, 32, 50, 18035, 18046, 50, Dec. 2012, [Peer-reviewed]
English, Dopaminergic (DAergic) neurons in the ventral tegmental area (VTA) play crucial roles in motivational control of behaviors, and their activity is regulated directly or indirectly via GABAergic neurons by extrinsic afferents from various sources, including the bed nucleus of the stria terminalis (BST). Here, the neurochemical composition of VTA-projecting BST neurons and their outputs to the VTA were studied in adult mouse brains. By combining retrograde tracing with fluorescence in situ hybridization for 67 kDa glutamate decarboxylase (GAD67) and vesicular glutamate transporters (VGluTs), VTA-targeting BST neurons were classified into GAD67-positive (GAD67(+))/VGluT3-negative (VGluT3(-)), GAD67(+)/VGluT3(+), and VGluT2(+) neurons, of which GAD67(+)/VGluT3(-) neurons constituted the majority (∼90%) of VTA-projecting BST neurons. GABAergic efferents from the BST formed symmetrical synapses on VTA neurons, which were mostly GABAergic neurons, and expressed GABA(A) receptor α1 subunit on their synaptic and extrasynaptic membranes. In the VTA, VGluT3 was detected in terminals expressing vesicular inhibitory amino acid transporter (VIAAT), plasmalemmal serotonin transporter, or neither. Of these, VIAAT(+)/VGluT3(+) terminals, which should include those from GAD67(+)/VGluT3(+) BST neurons, formed symmetrical synapses. When single axons from VGluT3(+) BST neurons were examined, almost all terminals were labeled for VIAAT, whereas VGluT3 was often absent from terminals with high VIAAT loads. VGluT2(+) terminals in the VTA exclusively formed asymmetrical synapses, which expressed AMPA receptors on postsynaptic membrane. Therefore, the major mode of the BST-VTA projection is GABAergic, and its activation is predicted to disinhibit VTA DAergic neurons. VGluT2(+) and VGluT3(+) BST neurons further supply additional projections, which may principally convey excitatory or inhibitory inputs, respectively, to the VTA. - Presynaptically Released Cbln1 Induces Dynamic Axonal Structural Changes by Interacting with GluD2 during Cerebellar Synapse Formation
Aya Ito-Ishida, Taisuke Miyazaki, Eriko Miura, Keiko Matsuda, Masahiko Watanabe, Michisuke Yuzaki, Shigeo Okabe
NEURON, 76, 3, 549, 564, Nov. 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 - GABAergic Inhibition Regulates Developmental Synapse Elimination in the Cerebellum
Hisako Nakayama, Taisuke Miyazaki, Kazuo Kitamura, Kouichi Hashimoto, Yuchio Yanagawa, Kunihiko Obata, Kenji Sakimura, Masahiko Watanabe, Masanobu Kano
NEURON, 74, 2, 384, 396, Apr. 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 - Postsynaptic P/Q-type Ca2+ channel in Purkinje cell mediates synaptic competition and elimination in developing cerebellum
Kouichi Hashimoto, Mika Tsujita, Taisuke Miyazaki, Kazuo Kitamura, Maya Yamazaki, Hee-Sup Shin, Masahiko Watanabe, Kenji Sakimura, Masanobu Kano
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 108, 24, 9987, 9992, Jun. 2011, [Peer-reviewed]
English, Scientific journal - Development of an anatomical technique for visualizing the mode of climbing fiber innervation in Purkinje cells and its application to mutant mice lacking GluRδ2 and Cav2.1
Taisuke Miyazaki, Masahiko Watanabe
Anatomical Science International, 86, 1, 10, 18, 1, Mar. 2011, [Peer-reviewed]
English - 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]
English, Scientific journal - Cellular expression and subcellular localization of secretogranin II in the mouse hippocampus and cerebellum.
Miyazaki T, Yamasaki M, Uchigashima M, Matsushima A, Watanabe M
The European journal of neuroscience, 33, 1, 82, 94, 1, Jan. 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] - Glutamate transporter GLAST is essential for cytodifferentiation of Bergmann glia and maintenance of excitatory synaptic wiring in the cerebellum
Miyazaki Taisuke, Yamasaki Miwako, Hashimoto Kouichi, Shimamoto Keiko, Kohda Kazuhisa, Yuzaki Michisuke, Tanaka Kohichi, Kano Masanobu, Watanabe Masahiko
NEUROSCIENCE RESEARCH, 71, E63, 2011, [Peer-reviewed] - Developmental switching of perisomatic innervation from climbing fibers to basket cell fibers in developing cerebellar purkinje cells
Ichikawa Ryoichi, Yamasaki Miwako, Miyazaki Taisuke, Tatsumi Haruyuki, Watanabe Masahiko
NEUROSCIENCE RESEARCH, 71, E215, 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] - 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 - Cbln1 Is a Ligand for an Orphan Glutamate Receptor delta 2, a Bidirectional Synapse Organizer
Keiko Matsuda, Eriko Miura, Taisuke Miyazaki, Wataru Kakegawa, Kyoichi Emi, Sakae Narumi, Yugo Fukazawa, Aya Ito-Ishida, Tetsuro Kondo, Ryuichi Shigemoto, Masahiko Watanabe, Michisuke Yuzaki
SCIENCE, 328, 5976, 363, 368, Apr. 2010, [Peer-reviewed]
English, Scientific journal - 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] - P/Q type voltage dependent Ca2+ channel is crucial for early postnatal development of climbing fiber to Purkinje cell synapse
Hashimoto Kouichi, Tsujita Mika, Kitamura Kazuo, Miyazaki Taisuke, Yamazaki Maya, Shin Hee-Sup, Watanabe Masahiko, Sakimura Kenji, Kano Masanobu
NEUROSCIENCE RESEARCH, 68, E37, E38, 2010, [Peer-reviewed] - Functional Coupling between mGluR1 and Ca(v)3.1 T-Type Calcium Channels Contributes to Parallel Fiber-Induced Fast Calcium Signaling within Purkinje Cell Dendritic Spines
Michael E. Hildebrand, Philippe Isope, Taisuke Miyazaki, Toshitaka Nakaya, Esperanza Garcia, Anne Feltz, Toni Schneider, Juergen Hescheler, Masanobu Kano, Kenji Sakimura, Masahiko Watanabe, Stephane Dieudonne, Terrance P. Snutch
JOURNAL OF NEUROSCIENCE, 29, 31, 9668, 9682, Aug. 2009, [Peer-reviewed]
English, Scientific journal - The N-Terminal Domain of GluD2 (GluR delta 2) Recruits Presynaptic Terminals and Regulates Synaptogenesis in the Cerebellum In Vivo
Wataru Kakegawa, Taisuke Miyazaki, Kazuhisa Kohda, Keiko Matsuda, Kyoichi Emi, Junko Motohashi, Masahiko Watanabe, Michisuke Yuzaki
JOURNAL OF NEUROSCIENCE, 29, 18, 5738, 5748, May 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] - Spinocerebellar ataxia type 6 knockin mice develop a progressive neuronal dysfunction with age-dependent accumulation of mutant Ca(v)2.1 channels
Kei Watase, Curtis F. Barrett, Taisuke Miyazaki, Taro Ishiguro, Kinya Ishikawa, Yuanxin Hu, Toshinori Unno, Yaling Sun, Sayumi Kasai, Masahiko Watainabe, Christopher M. Gomez, Hidehiro Mizusawa, Richard W. Tsien, Huda Y. Zoghbi
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 105, 33, 11987, 11992, Aug. 2008, [Peer-reviewed]
English, Scientific journal - Cerebellar pathology in transgenic mice expressing the pseudorabies virus immediate-early protein IE180
Yukiko Tomioka, Taisuke Miyazaki, Satoshi Taharaguchi, Saori Yoshino, Masami Morimatsu, Toshimitsu Uede, Etsuro Ono, Masahiko Watanabe
EUROPEAN JOURNAL OF NEUROSCIENCE, 27, 8, 2115, 2132, Apr. 2008, [Peer-reviewed]
English, Scientific journal - Differential regulation of synaptic plasticity and cerebellar motor learning by the C-terminal PDZ-binding motif of GluR delta 2
Wataru Kakegawa, Taisuke Miyazaki, Kyoichi Emi, Keiko Matsuda, Kazuhisa Kohda, Junko Motohashi, Masayoshi Mishina, Shigenori Kawahara, Masahiko Watanabe, Michisuke Yuzaki
JOURNAL OF NEUROSCIENCE, 28, 6, 1460, 1468, Feb. 2008, [Peer-reviewed]
English, Scientific journal - Effects of FAK ablation on cerebellar foliation, Bergmann glia positioning and climbing fiber territory on Purkinje cells
Fumihiro Watanabe, Taisuke Miyazaki, Tomonori Takeuchi, Masahiro Fukaya, Takanori Nomura, Shigeru Noguchi, Hisashi Mori, Kenji Sakimura, Masahiko Watanabe, Masayoshi Mishina
EUROPEAN JOURNAL OF NEUROSCIENCE, 27, 4, 836, 854, Feb. 2008, [Peer-reviewed]
English, Scientific journal - IQ-ArfGEF/BRAG1 is a guanine nucleotide exchange factor for Arf6 that interacts with PSD-95 at postsynaptic density of excitatory synapses
Hiroyuki Sakagami, Masashi Sanda, Masahiro Fukaya, Taisuke Miyazaki, Jun Sukegawa, Teruyuki Yanagisawa, Tatsuo Suzuki, Kohji Fukunaga, Masahiko Watanabe, Hisatake Kondo
NEUROSCIENCE RESEARCH, 60, 2, 199, 212, Feb. 2008, [Peer-reviewed]
English, Scientific journal - Modulation of inhibitory synaptic transmission in cerebellar Purkinje cells by CbIn1
Ishida Aya, Matsuda Keiko, Miyazaki Taisuke, Miura Eriko, Iijima Takatoshi, Kondo Tetsuro, Watanabe Masahiko, Yuzaki Michisuke
NEUROSCIENCE RESEARCH, 61, S78, 2008, [Peer-reviewed] - Abnormal features in mutant cerebellar Purkinje cells lacking junctophilins
Atsushi Ikeda, Taisuke Miyazaki, Sho Kakizawa, Yasushi Okuno, Soken Tsuchiya, Akira Myomoto, Shin-Ya Saito, Tetsuji Yamamoto, Tetsuo Yamazaki, Masamitsu Iino, Gozoh Tsujimoto, Masahiko Watanabe, Hiroshi Takeshima
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 363, 3, 835, 839, Nov. 2007, [Peer-reviewed]
English, Scientific journal - CD3 and immunoglobulin G Fc receptor regulate cerebellar functions
Kazuhiro Nakamura, Hirokazu Hirai, Takashi Torashima, Taisuke Miyazaki, Hiromichi Tsurui, Yan Xiu, Mareki Ohtsuji, Qing Shun Lin, Kazuyuki Tsukamoto, Hiroyuki Nishimura, Masao Ono, Masahiko Watanabe, Sachiko Hirose
MOLECULAR AND CELLULAR BIOLOGY, 27, 14, 5128, 5134, Jul. 2007, [Peer-reviewed]
English, Scientific journal - Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity
Sho Kakizawa, Yasushi Kishimoto, Kouichi Hashimoto, Taisuke Miyazaki, Kazuharu Furutani, Hidemi Shimizu, Masahiro Fukaya, Miyuki Nishi, Hiroyuki Sakagami, Atsushi Ikeda, Hisatake Kondo, Masanobu Kano, Masahiko Watanabe, Masamitsu Iino, Hiroshi Takeshima
EMBO JOURNAL, 26, 7, 1924, 1933, Apr. 2007, [Peer-reviewed]
English, Scientific journal - Ca2+ permeability of the channel pore is not essential for the delta 2 glutamate receptor to regulate synaptic plasticity and motor coordination
Wataru Kakegawa, Taisuke Miyazaki, Hirokazu Hirai, Junko Motohashi, Masayoshi Mishina, Masahiko Watanabe, Michisuke Yuzaki
JOURNAL OF PHYSIOLOGY-LONDON, 579, 3, 729, 735, Mar. 2007, [Peer-reviewed]
English, Scientific journal - GLAST is essential for cytological differentiation of Bergmann glia and climbing fiber monoinnervation by suppressing local ectopic innervation
Miyazaki Taisuke, Tanaka Kouichi, Watanabe Masahiko
NEUROSCIENCE RESEARCH, 58, S132, 2007, [Peer-reviewed] - Functional uncoupling between Ca2+ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins
Shigeki Moriguchi, Miyuki Nishi, Shinji Komazaki, Hiroyuki Sakagami, Taisuke Miyazaki, Haruko Masumiya, Shin-ya Saito, Masahiko Watanabe, Hisatake Kondo, Hiromu Yawo, Kohji Fukunaga, Hiroshi Takeshima
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 103, 28, 10811, 10816, Jul. 2006, [Peer-reviewed]
English, Scientific journal - Disturbance of cerebellar synaptic maturation in mutant mice lacking BSRPs, a novel brain-specific receptor-like protein family
Taisuke Miyazaki, Kouichi Hashimoto, Atsushi Uda, Hiroyuki Sakagami, Yoshitaka Nakamura, Shin-ya Saito, Miyuki Nishi, Hideaki Kume, Akira Tohgo, Izumi Kaneko, Hisatake Kondo, Kohji Fukunaga, Masanobu Kano, Masahiko Watanabe, Hiroshi Takeshima
FEBS LETTERS, 580, 17, 4057, 4064, Jul. 2006, [Peer-reviewed]
English, Scientific journal - Impaired cerebellar functions in mutant mice lacking DNER
A Tohgo, M Eiraku, T Miyazaki, E Miura, S Kawaguchi, M Nishi, M Watanabe, T Hirano, M Kengaku, H Takeshima
MOLECULAR AND CELLULAR NEUROSCIENCE, 31, 2, 326, 333, Feb. 2006, [Peer-reviewed]
English, Scientific journal - Morphological analysis of multiple climbing fiber innervation in PKC gamma-deficient mouse
Yamasaki Miwako, Hashimoto Kouichi, Miyazaki Taisuke, Watanabe Masahiko, Kano Masanobu
NEUROSCIENCE RESEARCH, 55, S174, 2006, [Peer-reviewed] - Maintenance of presynaptic function by AMPA receptor-mediated excitatory postsynaptic activity in adult brain
S Kakizawa, T Miyazaki, D Yanagihara, M Iino, M Watanabe, M Kano
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 102, 52, 19180, 19185, Dec. 2005, [Peer-reviewed]
English, Scientific journal - Cbln1 is essential for synaptic integrity and plasticity in the cerebellum
H Hirai, Z Pang, DH Bao, T Miyazaki, LY Li, E Miura, J Parris, YQ Rong, M Watanabe, M Yuzaki, JI Morgan
NATURE NEUROSCIENCE, 8, 11, 1534, 1541, Nov. 2005, [Peer-reviewed]
English, Scientific journal - Differential roles of glial and neuronal glutamate transporters in Purkinje cell synapses
Y Takayasu, M Iino, W Kakegawa, H Maeno, K Watase, K Wada, D Yanagihara, T Miyazaki, O Komine, M Watanabe, K Tanaka, S Ozawa
JOURNAL OF NEUROSCIENCE, 25, 38, 8788, 8793, Sep. 2005, [Peer-reviewed]
English, Scientific journal - Control of synaptic connection by glutamate receptor delta 2 in the adult cerebellum
T Takeuchi, T Miyazaki, M Watanabe, H Mori, K Sakimura, M Mishina
JOURNAL OF NEUROSCIENCE, 25, 8, 2146, 2156, Feb. 2005, [Peer-reviewed]
English, Scientific journal - Rescue of abnormal phenotypes of the delta 2 glutamate receptor-null mice by mutant delta 2 transgenes
H Hirai, T Miyazaki, W Kakegawa, S Matsuda, M Mushina, M Watanabe, M Yuzaki
EMBO REPORTS, 6, 1, 90, 95, Jan. 2005, [Peer-reviewed]
English, Scientific journal - Defective function of GABA-containing synaptic vesicles in mice lacking the AP-3B clathrin adaptor
F Nakatsu, M Okada, F Mori, N Kumazawa, H Iwasa, G Zhu, Y Kasagi, H Kamiya, A Harada, K Nishimura, A Takeuchi, T Miyazaki, M Watanabe, S Yuasa, T Manabe, K Wakabayashi, S Kaneko, T Saito, H Ohno
JOURNAL OF CELL BIOLOGY, 167, 2, 293, 302, Oct. 2004, [Peer-reviewed]
English, Scientific journal - 成熟マウス小脳におけるシナプス後膜AMPA受容体の活動に依存したシナプス前終末の機能維持(Postsynaptic AMPA receptor activity maintains presynaptic function in the adult cerebellum)
柿澤 昌, 宮崎 太輔, 飯野 正光, 渡辺 雅彦, 狩野 方伸
神経化学, 43, 2-3, 470, 470, 日本神経化学会, Aug. 2004
English - P/Q-type Ca2+ channel alpha 1A regulates synaptic competition on developing cerebellar Purkinje cells
T Miyazaki, K Hashimoto, HS Shin, M Kano, M Watanabe
JOURNAL OF NEUROSCIENCE, 24, 7, 1734, 1743, Feb. 2004, [Peer-reviewed]
English, Scientific journal - Possible involvement of AP-3B in VGAT-associated inhibitory synaptic function
Nakatsu, F, Okada, M, Mori, F, Kumazawa, N, Iwasa, H, Zhu, G, Kasagi, Y, Kamiya, H, Harada, A, Nishimura, K, Takeuchi, A, Miyazaki, T, Watanabe, M, Yuasa, S, Manabe, T, Wakabayashi, K, Kaneko, S, Saito, T, Ohno, H
MOLECULAR BIOLOGY OF THE CELL, 15, 221A, 221A, 2004, [Peer-reviewed] - Subtype switching of vesicular glutamate transporters at parallel fibre-Purkinje cell synapses in developing mouse cerebellum
T Miyazaki, M Fukaya, H Shimizu, M Watanabe
EUROPEAN JOURNAL OF NEUROSCIENCE, 17, 12, 2563, 2572, Jun. 2003, [Peer-reviewed]
English, Scientific journal - Distal extension of climbing fiber territory and multiple innervation caused by aberrant wiring to adjacent spiny branchlets in cerebellar Purkinje cells lacking glutamate receptor delta 2
R Ichikawa, T Miyazaki, M Kano, T Hashikawa, H Tatsumi, K Sakimura, M Mishina, Y Inoue, M Watanabe
JOURNAL OF NEUROSCIENCE, 22, 19, 8487, 8503, Oct. 2002, [Peer-reviewed]
English, Scientific journal - B2 exon splicing of nonmuscle myosin heavy chain IIB is differently regulated in developing and adult rat brain
Miyazaki, T, Watanabe, M, Yamagishi, A, Takahashi, M
Neuroscience Research, 37, 4, 299, 306, 2000, [Peer-reviewed]
Two isoforms of nonmuscle myosin heavy chain IIB (MHC-IIB) are generated by alternative splicing; MHC-IIB(B2) differs from MHC-IIB(Delta B2) by the insertion of B2 exon cassette near the actin binding region. Here we examined expressions of the two splice variants in developing and adult rat brains by in situ hybridization with isoform-specific oligonucleotide probes. In adult, MHC-IIB(Delta B2) mRNA was highly expressed in neurons of the cerebral cortex, hippocampus, and cerebellum, whereas MHC-IIB(B2) mRNA was mainly distributed in the brainstem and cerebellum, with the highest level in Purkinje cells. During development, MHC-IIB(Delta B2) mRNA was predominantly expressed in various regions of embryonic and neonatal brains, whereas MHC-IIB(B2) mRNA was low during embryonic stages. Up-regulation of MHC-IIB(B2) started in the cerebellum during early postnatal stages when dendritogenesis and synaptogenesis occur actively in Purkinje cells. We further employed immunofluorescence using two antibodies (one recognizing both splicing variants and another specific to MHC-IIB(B2)), and found similar and dense localization in cell bodies and dendrites of Purkinje cells. Therefore, splicing of the B2 exon cassette undergoes distinct temporal and spatial regulations in the brain in vivo, and the different exon usage seems unlikely to affect the somato-dendritic localization of MHC-IIB. (C) 2000 Elsevier Science Ireland Ltd and Japan Neuroscience Society. All rights reserved.
Other Activities and Achievements
- 発達期マウス小脳登上線維-プルキンエ細胞投射系における勝者・敗者シナプスの分子解剖学的な分化過程
新田麻子, 山崎美和子, 今野幸太郎, 宮崎太輔, 渡辺雅彦, 日本解剖学会総会・全国学術集会抄録集(CD-ROM), 129th, 2024 - 新規カルシウム放出機構「一酸化窒素依存的カルシウム放出」と小脳依存性運動学習への関与
柿澤昌, 岸本泰司, 宮崎太輔, 田中碧, 村山尚, 渡辺雅彦, 飯野正光, 竹島浩, 日本NO学会学術集会プログラム抄録集, 15th, 52, 12 Jun. 2015
Japanese - Involvement of Nitric oxide-induced calcium release in extinction of cerebellum-dependent motor learning
Sho Kakizawa, Yasushi Kishimoto, Taisuke Miyazaki, Midori Tanaka, Takashi Murayama, Masahiko Watanabe, Masamitsu Iino, Hiroshi Takeshima, JOURNAL OF PHARMACOLOGICAL SCIENCES, 124, 100P, 100P, 2014
English, Summary international conference - Cav2.1カルボキシル末端細胞質内ドメインの病態生理学的意義の検討
相川 知徳, 宮崎 太輔, 三國 貴康, 重本 隆一, 若森 実, 狩野 方伸, 渡邊 雅彦, 水澤 英洋, 渡瀬 啓, 臨床神経学, 53, 12, 1495, 1495, Dec. 2013
(一社)日本神経学会, Japanese - The active zone protein CAST regulates synaptic vesicle recycling and quantal size
Kobayashi S, Hida Y, Ishizaki H, Inoue E, Tanaka-Okamoto M, Yamasaki M, Miyazaki T, Fukuya M, Kitajima I, Takai Yoshimi, Watanabe M, Ohtsuka T, Manabe T, J Physiol Sci, 63, S67, 2013
English, Introduction other - 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 - The maintenance of Purkinje axons by an RNA-binding protein HuC in adult cerebellum
Kyoko Kakumoto, Taisuke Miyazaki, Masahiko Watanabe, Robert Darnell, Hirotaka Okano, Hideyuki Okano, NEUROSCIENCE RESEARCH, 71, E95, E96, 2011
English, Summary international conference - Postsynaptic P/Q type voltage-dependent Ca2+ channel is involved in refinement of cerebellar climbing fiber to Purkinje cell synapses in early postnatal development
Kouichi Hashimoto, Mika Tsujita, Taisuke Miyazaki, Kazuo Kitamura, Maya Yamazaki, Shin Hee-sup, Masahiko Watanabe, Kenji Sakimura, Masanobu Kano, NEUROSCIENCE RESEARCH, 71, E322, E322, 2011
English, Summary international conference - Neuroanatomical Studies on Molecular Mechanisms Underlying Hetero- and Homosynaptic Competitions in Cerebellar Synaptic Circuit Development
MIYAZAKI T., 解剖學雜誌, 85, 3, 115, 116, 01 Sep. 2010
Japanese - 小脳回路 発達と可塑性の最前線 登上線維の発達過程におけるP/Q型電位依存性カルシウムチャネルの役割(Cellebellar circuitry: Cutting-edge of development and plasticity P/Q type voltage dependent Ca2+ channel is crucial for early postnatal development of climbing fiber to Purkinje cell synapse)
橋本 浩一, 辻田 実加, 喜多村 和郎, 宮崎 太輔, 山崎 真弥, Shin Hee-Sup, 渡辺 雅彦, 崎村 建司, 狩野 方伸, 神経化学, 49, 2-3, 461, 461, Aug. 2010
日本神経化学会, English - The maintenance of Purkinje axons by HuC in adult cerebellum
Kyoko Kakumoto, Taisuke Miyazaki, Masahiko Watanabe, Robert B. Darnell, Hirotaka James Okano, Hideyuki Okano, NEUROSCIENCE RESEARCH, 68, E61, E61, 2010
English, Summary international conference - P/Q type voltage-dependent Ca2+ channel is required for refinement of climbing fiber to Purkinje cell synapse in early postnatal development
Kouichi Hashimoto, Mika Tsujita, Taisuke Miyazaki, Maya Yamazaki, Kazuo Kitamura, Hee-sup Shin, Masahiko Watanabe, Kenji Sakimura, Masanobu Kano, JOURNAL OF PHYSIOLOGICAL SCIENCES, 60, S83, S83, 2010
English, Summary international conference - Analysis of physiological functions of cerebellar AMPA receptor subunits using a Purkinje cell-selective gene targeting system
Manabu Abe, Kouichi Hashimoto, Taisuke Miyazaki, Hirotsugu Azechi, Rie Natsume, Masahiko Watanabe, Masanobu Kano, Kenji Sakimura, NEUROSCIENCE RESEARCH, 68, E231, E231, 2010
English, Summary international conference - Cbln1 REGULATES INHIBITORY SYNAPTIC TRANSMISSION ON CEREBELLAR PURKINJE CELLS
Aya Ito-Ishida, Eriko Miura, Taisuke Miyazaki, Tetsushi Sadakata, Ritsuko Katoh-Semba, Keiko Matsuda, Teiichi Furuichi, Masahiko Watanabe, Michisuke Yuzaki, JOURNAL OF PHYSIOLOGICAL SCIENCES, 59, 145, 145, 2009
English, Summary international conference - GABAergic inhibition onto Purkinje cell soma is crucial for climbing fiber synapse elimination in developing cerebellum
Hisako Nakayama, Taisuke Miyazaki, Kouichi Hashimoto, Yuchio Yanagawa, Kunihiko Obata, Masahiko Watanabe, Masanobu Kano, NEUROSCIENCE RESEARCH, 65, S52, S52, 2009
English, Summary international conference - Loss of cerebellar granule cell AMPA receptors contributes to ataxia in stargazer mice
May Yamazaki, Masahiro Fukaya, Taisuke Miyazaki, Manabu Abe, Rie Natsume, Masahiko Watanabe, Kenji Sakimura, NEUROSCIENCE RESEARCH, 65, S140, S140, 2009
English, Summary international conference - DIFFERENTIAL REGULATION OF SYNAPSE FORMATION AND PLASTICITY BY GluR delta 2 IN THE CEREBELLUM
Wataru Kakegawa, Taisuke Miyazaki, Kazuhisa Kohda, Keiko Matsuda, Kyoichi Emi, Junko Motohashi, Masahiko Watanabe, Michisuke Yuzaki, JOURNAL OF PHYSIOLOGICAL SCIENCES, 59, 135, 135, 2009
English, Summary international conference - GLAST is essential to maintain climbing fiber monoinnervation and glial synapse enwrapping to cerebellar Purkinje cells
Taisuke Miyazaki, Kohichi Tanaka, Masahiko Watanabe, NEUROSCIENCE RESEARCH, 65, S44, S44, 2009
English, Summary international conference - Junctophilin-mediated functional crosstalk between ryanodine receptors and SK channels essential for long-term depression in the cerebellum
S. Kakizawa, Y. Kishimoto, K. Hashimoto, T. Miyazaki, K. Furutani, H. Shimizu, M. Fukaya, M. Nishi, H. Sakagami, A. Ikeda, H. Kondo, M. Kano, M. Watanabe, M. Iino, H. Takeshima, JOURNAL OF NEUROCHEMISTRY, 106, 50, 50, Jul. 2008
English, Summary international conference - Retardations in cerebellar foliation, the ectopic location of Bergmann glia, and altered climbing fiber territory on Purkinje cells by FAK ablation
Fumihiro Watanabe, Taisuke Miyazaki, Masahiro Fukaya, Tomonori Takeuchi, Kenji Sakimura, Masahiko Watanabe, Masayoshi Mishina, JOURNAL OF PHARMACOLOGICAL SCIENCES, 106, 82P, 82P, 2008
English, Summary international conference - Strength of GABAergic transmission influences climbing fiber synapse elimination during cerebellar development
Hisako Nakayama, Kouichi Hashimoto, Taisuke Miyazaki, Yuchio Yanagawa, Kunihiko Obata, Masahiko Watanabe, Masanobu Kano, NEUROSCIENCE RESEARCH, 58, S52, S52, 2007
English, Summary international conference - Protocadherin-alpha family in the olivo-cerebellar system; their isoform expression and loss of function analysis
You Kumode, Shun Hamada, Takashi Kitsukawa, Kouichi Hashimoto, Taisuke Miyazaki, Masanobu Kano, Masahiko Watanabe, Takeshi Yagi, NEUROSCIENCE RESEARCH, 58, S206, S206, 2007
English, Summary international conference - Junctophilin-mediated functional coupling of channels essential for cerebellar synaptic plasticity
Sho Kakizawa, Yasushi Kishimoto, Sin-ya Saito, Kouichi Hashimoto, Taisuke Miyazaki, Kazuharu Furutani, Miyuki Nishi, Hiroyuki Sakagami, Hisatake Kondo, Masanobu Kano, Masahiko Watanabe, Masamitsu Iino, Hiroshi Takeshima, JOURNAL OF PHARMACOLOGICAL SCIENCES, 103, 68P, 68P, 2007
English, Summary international conference - GLAST is essential for cytological differentiation of Bergmann glia and climbing fiber monoinnervation by suppressing local ectopic innervation
Taisuke Miyazaki, Kohichi Tanaka, Masahiko Watanabe, NEUROSCIENCE RESEARCH, 55, S174, S174, 2006
English, Summary international conference - Ca2+ influx through delta 2 glutamate receptors is not required for cerebellar functions
Wataru Kakegawa, Taisuke Miyazaki, Hirokazu Hirai, Masayoshi Mishina, Masahiko Watanabe, Michisuke Yuzaki, NEUROSCIENCE RESEARCH, 55, S172, S172, 2006
English, Summary international conference - Impaired cerebellar climbing fiber innervation in the nervous system-specific FAK deficient mice
F Watanabe, T Miyazaki, M Fukaya, T Takeuchi, M Watanabe, M Mishina, JOURNAL OF PHARMACOLOGICAL SCIENCES, 100, 246P, 246P, 2006
English, Summary international conference - Control of synaptic connection by glutamate receptor delta 2 in the mature cerebellum
T Takeuchi, T Miyazaki, M Watanabe, H Mori, K Sakimura, M Mishina, JOURNAL OF PHARMACOLOGICAL SCIENCES, 97, 114P, 114P, 2005
English, Summary international conference - RNA神経生物学 ニューロンにおける転写後の世界 IP3 receptor type 1 mRNAの3末端非翻訳領域に結合し,その樹状突起への局在化及び小脳運動学習に関わるRNA結合タンパク質Hzf(RNA neurobiology: Posttranscriptional world in neurons:Hzf binds to IP3R1 mRNA and is required for dendritic mRNA localization and the motor learning in ce
飯島 崇利, 今井 貴雄, 高月 香菜子, 小倉 博雄, 宮崎 太輔, 岡野 洋尚, 川原 茂敬, 渡辺 雅彦, 桐野 豊, 岡野 栄之, 神経化学, 43, 2-3, 329, 329, Aug. 2004
日本神経化学会, English - Conditional ablation of glutamate receptor delta 2 induces synaptic rearrangements in mature cerebellum
T Takeuchi, T Miyazaki, M Watanabe, H Mori, K Sakimura, M Mishina, JOURNAL OF PHARMACOLOGICAL SCIENCES, 94, 65P, 65P, 2004
English, Summary international conference - Distal extension of climbing fiber territory and multiple innervation caused by aberrant wiring to adjacent spiny branchlets in cerebellar Purkinje cells lacking glutamate receptor GluRδ2
Ichikawa Ryoichi, Miyazaki Taisuke, Kano Masanobu, Hashikawa Tsutomu, Tatsumi Haruyuki, Sakimura Kenji, Mishina Masayoshi, Inoue Yoshiro, Watanabe Masahiko, The Journal of neuroscience : the official journal of the Society for Neuroscience, 22, 19, 8487, 8503, 01 Oct. 2002
Organized synapse formation on to Purkinje cell (PC) dendrites by parallel fibers (PFs) and climbing fibers (CFs) is crucial for cerebellar function. In PCs lacking glutamate receptor delta2 (GluRdelta2), PF synapses are reduced in number, numerous free spines emerge, and multiple CF innervation persists to adulthood. In the present study, we conducted anterograde and immunohistochemical labelings to investigate how CFs innervate PC dendrites under weakened synaptogenesis by PFs. In the GluRdelta2 knock-out mouse, CFs were distributed in the molecular layer more closely to the pial surface compared with the wild-type mouse. Serial electron microscopy demonstrated that CFs in the knock-out mouse innervated all spines protruding from proximal dendrites of PCs, as did those in the wild-type mouse. In the knock-out mouse, however, CF innervation extended distally to spiny branchlets, where nearly half of the spines were free of innervation in contrast to complete synapse formation by PFs in the wild-type mouse. Furthermore, from the end point of innervation, CFs aberrantly jumped to form ectopic synapses on adjacent spiny branchlets, whose proximal portions were often innervated by different CFs. Without GluRdelta2, CFs are thus able to expand their territory along and beyond dendritic trees of the target PC, resulting in persistent surplus CFs by innervating the distal dendritic segment. We conclude that GluRdelta2 is essential to restrict CF innervation to the proximal dendritic segment, by which territorized innervation by PFs and CFs is properly structured and the formation of excess CF wiring to adjacent PCs is suppressed., Society for Neuroscience, English
Lectures, oral presentations, etc.
- Carbonic anhydrase related protein Car8 is essential for the establishment of cerebellar neuronal circuit, regulating precise matching of pre and postsynapse in Purkinje cell.
Miyazaki T, Yamasaki M, Sakimura K, Watanabe M
第126回 日本解剖学会総会・全国学術集会 第98回 日本生理学会大会合同大会, 28 Mar. 2021 - 小脳抑制性介在ニューロンルガロ細胞の帯状構造特異的な入出力様式.
宮﨑太輔, 山崎美和子, 田中謙二, 渡辺雅彦
生理学研究所研究会 自閉症、てんかんの病態原理に関与するシナプス制御・神経回路機構, 02 Feb. 2021
[Invited] - Principal rule of neurotransmitter receptor localization at synapse
Taisuke Miyazaki
Current Trends and Future Directions of Synapse-Circuit Plasticity Research, 03 Sep. 2019, English, Oral presentation
[International presentation] - Compartmentalized input-output organization of cerebellar Lugaro cells, as revealed using knockin-mediated yellow cameleon reporter mice
Taisuke Miyazaki
第42回日本神経科学学会, 25 Jul. 2019, English, Oral presentation
[Domestic Conference] - "Morphological classification of cerebellar interneurons and their connections"
Taisuke Miyazaki
"Synaptic Transmission Synaptic Transmission Gordon Research Conference", 12 Aug. 2018, English, Poster presentation
[International presentation] - Calcineurin B1 subunit CNB1 in Purkinje cells regulates precise pre- and postsynaptic matching in inhibitory synapse formation
Taisuke Miyazaki
The innovative progress of neuroscientific research through the use of advanced animal models, 10 Feb. 2018, English, Poster presentation
[International presentation] - カルシウムチャネルCav2.1は成体期プルキンエ細胞の生存、バンド状発現、神経支配テリトリーの維持に不可欠である
宮崎太輔
第63回東北・北海道連合支部学術集会, 09 Sep. 2017, Japanese, Oral presentation
弘前大学大学院保健学研究科E棟6階(弘前大学医学部保健学科), [Domestic Conference] - Calcineurin B1 subunit is essential for climbing fiber mono-innervation and inhibitory synapse formation in Purkinje cells
MIYAZAKI Taisuke, SAKIMURA Kenji, WATANABE Masahiko
日本解剖学会総会・全国学術集会講演プログラム・抄録集, 2017, English - 小脳登上線維と抑制性介在細胞間における非シナプス性結合と選択的分子発現
山崎美和子, 深谷昌弘, 宋暁紅, 内ケ島基政, 今野幸太郎, 宮崎太輔, 渡辺雅彦
日本解剖学会総会・全国学術集会講演プログラム・抄録集, 2016, Japanese - Neuroanatomical properties of cerebellar interneuron Lugaro cells using with GFP-expressing transgenic mice line
MIYAZAKI Taisuke, TANAKA Kenji F, WATANABE Masahiko
日本解剖学会総会・全国学術集会講演プログラム・抄録集, 2016, English - 新規カルシウム放出機構「一酸化窒素依存的カルシウム放出」と小脳依存性運動学習への関与
柿澤昌, 岸本泰司, 宮崎太輔, 田中碧, 村山尚, 渡辺雅彦, 飯野正光, 竹島浩
日本NO学会学術集会プログラム抄録集, 12 Jun. 2015, Japanese - Morphological analysis of Purkinje cell-specific calcineurin B1 subunit KO mice
MIYAZAKI Taisuke, SAKIMURA Kenji, WATANABE Masahiko
J Physiol Sci, 2015, English - Calcineurin B1 subunit expressed in Purkinje cell is essential for the formation of excitatory and inhibitory cerebellar neuronal network
Taisuke Miyazaki, Kenji Sakimura, Masahiko Watanabe
第38回日本神経科学大会, 2015, Japanese
神戸国際会議場 (兵庫県 神戸市) - BDNF derived from Purkinje cell regulates synapse elimination in the developing cerebellum
CHOO Myeong Jeong, MIYAZAKI Taisuke, YAMASAKI Maya, TANIMURA Asami, UESAKA Naofumi, WATANABE Masahiko, SAKIMURA Kenji, KANO Masanobu
J Physiol Sci, 2014, English - Cav2.1カルボキシル末端細胞質内ドメインの病態生理学的意義の検討
相川知徳, 宮崎太輔, 三國貴康, 重本隆一, 若森実, 狩野方伸, 渡邊雅彦, 水澤英洋, 渡瀬啓
日本神経学会学術大会プログラム・抄録集, 2013, Japanese - 蛍光タンパク発現モデルマウスを用いた小脳ルガロ細胞の形態学
宮崎太輔, 渡辺雅彦
日本解剖学会総会・全国学術集会講演プログラム・抄録集, 2013, Japanese
サンポートホール高松 (香川県 高松市) - 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, 01 Apr. 2012, Japanese - 発達期小脳登上線維‐プルキンエ細胞間シナプス除去への抑制性シナプス伝達の関与
中山寿子, 宮崎太輔, 橋本浩一, 柳川右千夫, 小幡邦彦, 崎村建司, 渡辺雅彦, 狩野方伸
日本生理学雑誌, 01 Mar. 2012, Japanese - Neuroanatomical Studies on Molecular Mechanisms Underlying Hetero- and Homosynaptic Competitions in Cerebellar Synaptic Circuit Development
MIYAZAKI T
解剖學雜誌, 01 Sep. 2010, Japanese - P/Q type voltage dependent Ca2+ channel is crucial for early postnatal development of climbing fiber to Purkinje cell synapse
HASHIMOTO Kouichi, TSUJITA Mika, KITAMURA Kazuo, MIYAZAKI Taisuke, YAMAZAKI Maya, SHIN Hee‐Sup, WATANABE Masahiko, SAKIMURA Kenji, KANO Masanobu
神経化学, 01 Aug. 2010, English - Ablation of glutamate receptor GluD2 in adult Purkinje cells causes multiple innervation of climbing fibers by ectopic innervation of transverse collaterals
○Taisuke Miyazaki, Miwako Yamasaki, Tomonori Takeuchi, Kenji Sakimura, Masayoshi Mishina, Masahiko Watanabe
第33回日本神経科学大会, 01 Aug. 2010, English
神戸コンベンションセンター(兵庫県 神戸市) - グルタミン酸受容体GluD2は側方側枝による異所性支配を抑制し,登上線維単一支配の維持に関わっている
宮崎太輔, 山崎美和子, 竹内倫徳, 三品昌美, 渡辺雅彦
解剖学雑誌, Mar. 2010, Japanese - GluD2 is essential for maintenance of climbing fiber-Purkinje cell mono-innervation by suppressing ectopic innervation of transverse branches.
Taisuke Miyazaki, Miwako Yamasaki, Tomonori Takeuchi, Kenji Sakimura, Masayoshi Mishina, Masahiko Watanabe
第115回日本解剖学会総会・全国学術集会, 2010, Japanese
岩手県民会館 (岩手県 盛岡市) - Immunohistochemical analysis of Secretogranin II (SgII) in the cerebellum and hippocampus
宮崎 太輔, 渡辺 雅彦
第114回 日本解剖学会総会・全国学術集会, Mar. 2009, Japanese
岡山理科大学 (岡山県 岡山市) - Immunohistochemical analysis of Secretogranin II (SgII) in the cerebellum and hippocampus
宮崎 太輔, 渡辺 雅彦
第114回 日本解剖学会総会・全国学術集会, 2009, Japanese
岡山理科大学 (岡山県 岡山市) - SCA6ノックインマウス表現型の経時的検討
渡瀬啓, BARRET Curtis, 宮崎太輔, 海野敏紀, 石川欽也, 笠井沙由美, 渡辺雅彦, 水澤英洋, TSIEN Richard, ZOGHBI Huda
日本神経学会総会プログラム・抄録集, 2009, Japanese - GLAST is essential to maintain climbing fiber monoinnervation and glial synapse enwrapping to cerebellar Purkinje cells
Taisuke Miyazaki, Kouichi Tanaka, Masahiko Watanabe
第32回日本神経科学大会, 2009, Japanese
名古屋国際会議場 (愛知県 名古屋市) - 仮性狂犬病ウイルス前初期蛋白IE180発現マウスにおける小脳形成不全の病理組織学的解析
富岡幸子, 宮崎太輔, 田原口智士, 森松正美, 渡辺雅彦, 小野悦郎
日本獣医学会学術集会講演要旨集, 07 Mar. 2008, Japanese - GluRd2 is essential for maintenance of climbing fiber-Purkinje cell mono-innervation in adult mice.
第113回 日本解剖学会総会・全国学術集会, 2008, Japanese
大分大学 (大分県 大分市) - GLAST is essential for cytological differentiation of Bergmann glia and climbing fiber monoinnervation by suppressing local ectopic innervation
Taisuke Miyazaki, Kouichi Tanaka, Masahiko Watanabe
第31回日本神経科学大会, 2008, Japanese
東京国際フォーラム(東京) - GLAST分子欠損マウスにおけるバーグマングリアの形態分化異常および局所的な異所性プルキンエ細胞支配による登上線維多重支配
Taisuke Miyazaki, Masahiko Watanabe
第112回 日本解剖学会総会・全国学術集会, 2007, Japanese
大阪国際会議場(大阪府 大阪市) - GLAST分子欠損マウスにおけるバーグマングリアの形態分化異常および形態学的登上線維多重支配
Taisuke Miyazaki, Kouichi Tanaka, Masahiko Watanabe
第30回日本神経科学大会, 2007, Japanese
パシフィコ横浜(神奈川県 横浜市) - オーエスキー病ウイルスC末端欠失変異型前初期蛋白IE180発現マウスの解析
富岡幸子, 宮崎太輔, 田原口智士, 吉野さおり, 森松正美, 渡辺雅彦, 上出利光, 小野悦郎
日本獣医学会学術集会講演要旨集, 31 Aug. 2006, Japanese - GLAST分子欠損マウスにおける登上線維多重支配 の形態学的解析
Taisuke Miyazaki, Masahiko Watanabe
第111回 日本解剖学会総会・全国学術集会, 2006, Japanese
北里大学(神奈川県 相模原市) - GLAST分子欠損マウスにおけるバーグマングリアの形態分化異常および局所的な異所性プルキンエ細胞支配による登上線維多重支配
Taisuke Miyazaki, Masahiko Watanabe
第112回 日本解剖学会総会・全国学術集会, 2006, Japanese
大阪国際会議場(大阪府 大阪市) - Multiple climbing fiber innervation at proximal dendrite in GLAST-deficient mouse
Taisuke Miyazaki, Kouichi Tanaka, Masahiko Watanabe
第28回日本神経科学大会, 2005, Japanese
パシフィコ横浜(神奈川県 横浜市) - Excitatory and inhibitory innervation on to Purkinje cell soma in calcium channel ?1A subunit deficient mice
Taisuke Miyazaki, Kouichi Hashimoto, Hee-Sup Shin, Masanobu Kano, Masahiko Watanabe
第27回日本神経科学大会, 2004, Japanese
大阪国際会議場(大阪府 大阪市) - 発達小脳における2種類のグルタミン酸トランスポーターVGluT1およびVGluT2の発現変化
宮崎 太輔, 渡辺 雅彦
第108回 日本解剖学会総会・全国学術集会, 2003, Japanese
アクロス福岡(福岡県 福岡市) - プルキンエ細胞への興奮性入力終末における2種類の小胞膜グルタミン酸トランスポーター発現の発達変化
宮崎太輔, 深谷昌弘, 清水秀美, 渡辺雅彦
日本神経科学大会プログラム・抄録集, 07 Jul. 2002, Japanese
東京 - プルキンエ細胞への興奮性入力終末における2種類の小胞膜グルタミン酸トランスポーター発現の発達変化
宮崎 太輔, 深谷 昌弘, 清水 秀美, 渡辺 雅彦
第25回日本神経科学大会, 2002, Japanese
東京国際展示場 (東京) - ラット脳における非筋細胞II型ミオシン重鎖Bの発現と局在
宮崎 太輔, 渡辺 雅彦
第23回日本神経科学大会, 2000, Japanese
パシフィコ横浜(神奈川県 横浜市) - プルキンエ細胞への興奮性入力終末における2種類の小胞膜グルタミン酸トランスポーター発現の発達変化
宮崎 太輔, 深谷 昌弘, 清水 秀美, 渡辺 雅彦
第47回東北・北海道連合支部学術集会, 2000, Japanese
北海道大学 (北海道 札幌市) - Localization of myosin II-B(B2) in central nervous system tissue
MIYAZAKI Taisuke, TAKAHASHI Masayuki, HATAKEYAMA Dai, ITOH Etsuro, YAMAGISHI Akihiko
日本分子生物学会年会プログラム・講演要旨集, 01 Dec. 1998, Japanese - カルシウムチャネルalpha1Aサブユニット欠損マウスにおけるプルキンエ細胞興奮性シナプス回路網の変化
宮崎 太輔, 渡辺 雅彦
第49回東北・北海道連合支部学術集会, Japanese
岩手医科大学(岩手県 盛岡市) - GLAST分子欠損マウスにおける登上線維支配様式の光学顕微鏡的解析
宮崎 太輔, 渡辺 雅彦
第51回東北・北海道連合支部学術集会, Japanese
東北大学(宮城県 仙台市) - GLASTは登上線維単一支配の維持に必要である
宮崎 太輔, 山崎 美和子, 渡辺 雅彦
第54回東北・北海道連合支部学術集会, Japanese
ビックアイ市民交流プラザ(福島県 郡山市) - Glutamate transporter GLAST is essential for cytodifferentiation of Bergmann glia and maintenance of excitatory synaptic wiring in the cerebellum
Taisuke Miyazaki, Miwako Yamasaki, Kouichi Hashimoto, Keiko Shimamoto, Kazuhisa Kohda, Michisuke Yuzaki, Kohichi Tanaka, Masanobu Kano, Masahiko Watanabe
第34回日本神経科学大会, Japanese
パシフィコ横浜(神奈川県 横浜市) - 蛍光タンパク発現モデルマウスを用いた小脳ルガロ細胞に関する形態学解析
Taisuke Miyazaki
日本顕微鏡学会第70回記念学術講演会, Japanese
幕張メッセ(千葉県 幕張市) - プルキンエ細胞に発現するカルシニューリンCNB1サブユニットは小脳の興奮性および抑制性シナプス回路形成に重要である
宮崎 太輔, 崎村, 建司, 渡辺 雅彦
第61回東北・北海道連合支部学術集会, Japanese
盛岡市観光文化交流センター(岩手県 盛岡市) - Calcineurin B1 subunit is essential for climbing fiber mono-innervation and inhibitory synapse formation in cerebellar Purkinje cells
Taisuke Miyazaki, Kenji Sakimura, Masahiko Watanabe
第122回日本解剖学会総会全国学術集会, Japanese
長崎大学(長崎県 長崎市) - Cav2.1 is indispensable to maintain wiring, survival, and compartmentalized expression in adult cerebellar Purkinje cells
Taisuke Miyazaki, Miwako Yamasaki, Kenji Sakimura, Masahiko Watanabe
第39回日本神経科学大会, Japanese
パシフィコ横浜(神奈川県 横浜市) - ?Calcineurin B1 subunit in Purkinje cells regulates proper pre- and postsynaptic matching in GABAergic synapse formation
Taisuke Miyazaki, Kenji Sakimura, Masahiko Watanabe
第40回日本神経科学大会, Japanese
幕張メッセ(千葉県 幕張市)
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 - Verification of the functional involvement of P/Q-type calcium channels in synaptic pruning during adulthood
Grants-in-Aid for Scientific Research
01 Apr. 2021 - 31 Mar. 2025
渡辺 雅彦, 宮崎 太輔
令和3年度の研究活動において、成体期におけるプロゲステロン誘導剤投与によりてCav2.1遺伝子をプルキンエ細胞のみに選択的に欠損させるモデルマウスを作成した。令和4年度において、このモデルを用いて、成体期遺伝子欠損に伴う小脳の組織学的変化を光学顕微鏡と電子顕微鏡を用いて解析し、受精卵の段階から遺伝子を欠損する完全欠失型ノックアウトマウスの表現型とも一致した表現型を得たことから、Cav2.1は成体期においても、細胞死を抑止し近位樹状突起におけるスパイン形成を抑制する機能、すなわち近位樹状突起におけるシナプス刈り込みの促進する機能を果たしていることが明らかにした。
令和5年度においては、平行線維支配テリトリーと登上線維支配テリトリーの分離に関する解析に関する研究テーマに取り組んだ。まず、成体期欠損群とコントロール群の脳幹下オリーブ核に順行性神経トレーサーを注入して登上線維を蛍光標識し、登上線維が支
配するプルキンエ細胞樹状突起(カルビンジンで蛍光標識)上のテリトリーを可視化した。その結果、成体期欠損により登上背にに支配領域の近位退縮が誘導され、その後余剰な登上線維による多重支配が惹起された。一方、電子顕微鏡観察により平行線維シナプスの形成領域が本来の遠位樹状突起に限局せずに、近位部まで拡大していることを明らかにした。これにより、遠近方向に分離した登上線維と平行線維の支配テリトリーの境界形成において、成体期のP/Q型VDCCの機能により遠位に向かって移動し、登上線維支配の重複化が抑制されていることが明らかとなった。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 23K21350 - Functional involvement of P/Q-type calcium channel in synapse elimination in adult brains
Grants-in-Aid for Scientific Research
01 Apr. 2021 - 31 Mar. 2025
渡辺 雅彦, 宮崎 太輔
興奮性シナプス活動により、イオンチャネル型グルタミン酸受容体iGluRと代謝型グルタミン酸受容体mGluRの活性化が起こる。iGluR活性化による脱分極は、小脳プルキンエ細胞ではP/Q型カルシウムチャネルの活性化を介して細胞外からCa2+流入を誘導する。受精の段階からこの遺伝子欠損を有するヌル欠損マウスでは、シナプス刈込みに障害が生じて、登上線維と平行線維のテリトリー不分離と登上線維の多重支配が残存することを示してきた。本研究課題では、シナプス回路完成後の成体期においてもシナプス回路維持機構として機能しているかを、成体期に遺伝子欠損誘導を行えるモデルを作成して明らかにすることである。
新潟大学脳研究所の崎村建司名誉教授らが以前開発した、P/Q型VDCC のチャネル本体をコードするCav2.1遺伝子のfloxマウスと、プロゲステロン誘導剤(RU-486)依存的に活性化するCreリコンビナーゼをプルキンエ細胞選択的に発現するGluD2-CrePRマウスを入手する。亮者を交配して、Cav2.1flox/CrePRマウスラインを得た。生後2ヶ月令の成体マウスにRU-486を腹腔投与したものを成体期欠損群(Cav2.1-/CrePR)、溶剤のみを腹腔投与したものをコントロール群(Cav2.1flox/CrePR)とした。研究代表者が開発したCav2.1特異抗体を用いて免疫染色法を用いて検討したところ、 Cav2.1-/CrePRのプルキンエ細胞における Cav2.1 タンパクの有意な減少が誘導後1週から確認された。一方、Cav2.1flox/CrePでは Cav2.1 タンパクの発現の減少は認められなかった。したがって、神経回路が完成した成体期においてCav2.1遺伝子を欠損させるモデルマウスが完成したことを確認できた。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 21H02589 - 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
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 - プルキンエ細胞シナプス後部におけるカルシニューリン依存的入力認識機構の解明
科学研究費補助金(基盤研究(C))
Apr. 2017 - Mar. 2020
宮崎太輔
文部科学省, Principal investigator, Competitive research funding - 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 - Analysis for heterosynaptic competition between parallel and climbing fiber in mature Purkinje cells
Grants-in-Aid for Scientific Research
2014 - 2016
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, Principal investigator, Competitive research funding, 26460250 - Mechanism of climbing fiber synapse elimination at the developing Purkinje cell bodies
Grants-in-Aid for Scientific Research
2012 - 2013
MIYAZAKI Taisuke
In the developing cerebellum, climbing fiber (CF)-Purkinje cell (PC) synapses are eliminated from PC cell bodies, while the maturation of inhibitory interneurons such as basket (BC) or Lugaro cells (LC) proceeds. It has been unclear whether these excitatory and inhibitory inputs are directly correlated or not. In the present study, we investigated the process of CF-PC synapses elimination from PC cell bodies when the inhibitory interneurons are functionally disrupted. By analyses using with lentivirus and GFP-expressing reporter mouse, we found that somatic CF terminals were expelled by developing BC axons. In contrast to PC somata, CF terminals beneath PC layer increased in number during the second postnatal week, and CFs from multiple neuronal origins were found to innervate the somatodendritic domain of single LCs. Thus, the elimination of somatic CFs appears to proceed with the differentiation of inhibitory neuronal elements.
Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hokkaido University, Principal investigator, Competitive research funding, 24790185 - 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 - Morphological analysis for the maintenance of climbing fiber-Purkinje cell mono-innervation in the cerebellum
Grants-in-Aid for Scientific Research(若手研究(B))
2006 - 2008
Taisuke MIYAZAKI
小脳プルキンエ細胞 (PC)は、数十万本の平行線維 (PF)と1本の登上線維 (CF)による興奮性入力を受けている。幼若期のPCは複数のCFによる多重支配を受けているが、発達過程において余剰なCFは排除され、生後3週目までには一つのPCがただ1本のCFによって支配される単一支配が確立する。この単一支配化には、PFシナプス後部特異的に発現するグルタミン酸受容体GluRd2が重要であることが知られている。本研究では、誘導型GluRd2欠損マウスを用いて、CF-PC単一支配化の維持にGluRd2が関与しているかどうかを明らかにすべく行われた。誘導型GluRd2欠損マウスのCF-PC支配様式を、神経標識法および免疫組織化学法を用いて解析したところ、(1)分子欠損誘導後8週からCF多重支配が認められ、GluRd2欠損領域でCF支配領域の拡大が認められた、(2)分子欠損誘導後8週からtransverse branchと呼ばれるCF側枝が側方のPCに対して異所性支配を行い、CF-PC多重支配を引き起こしている様子が観察されたという2つの所見が得られた。以上の結果はGluRd2がCF側枝による側方支配を抑制することで成体期におけるCF-PC単一支配の維持に関わっていることを強く示唆するものであった。
Ministry of Education, Culture, Sports, Science and Technology, 若手研究(B), 北海道大学, Principal investigator, Competitive research funding, 18700335
syllabus
- 臨床実習Ⅱ(作), 2024年, 学士課程, 医学部
- 実験研究方法特論, 2024年, 修士課程, 保健科学院
- 医学総論, 2024年, 博士後期課程, 医学研究科
- 生体機能学基礎研究演習, 2024年, 修士課程, 保健科学院
- 生体機能学基礎研究特論, 2024年, 修士課程, 保健科学院
- 機能解剖学特論, 2024年, 修士課程, 保健科学院
- 先端リハビリテーション科学特講, 2024年, 博士後期課程, 保健科学院
- 先端リハビリテーション科学特講演習, 2024年, 博士後期課程, 保健科学院
- 臨床実習Ⅲ(作), 2024年, 学士課程, 医学部
- 臨床実習Ⅳ(作), 2024年, 学士課程, 医学部
- 保健解剖学演習, 2024年, 学士課程, 医学部
- 臨床実習Ⅰ(作), 2024年, 学士課程, 医学部
- リハビリテーション解剖学実習, 2024年, 学士課程, 医学部
- 保健解剖学, 2024年, 学士課程, 医学部
- 健康と社会, 2024年, 学士課程, 全学教育
- リハビリテーション解剖学Ⅱ, 2024年, 学士課程, 医学部
- 地域作業療法学実習, 2024年, 学士課程, 医学部
- 保健・医療概論, 2024年, 学士課程, 医学部
- 臨床実習Ⅱ(作), 2024年, 学士課程, 医学部
- 作業療法研究法, 2024年, 学士課程, 医学部
- 作業療法研究法演習, 2024年, 学士課程, 医学部