KEIO RESEARCHERS INFORMATION SYSTEM

Career 【 Display / hide 】

Career 【 Display / hide 】

• 2004.01

  -

  2007.03

  Keio University, School of Medicine,, Dept. of Physiology 1, 助手

• 2007.04

  -

  2014.09

  Keio University, School of Medicine,, Dept. of Physiology 1, 助教

• 2014.09

  -

  2016.09

  Keio University, School of Medicine,, Dept. of Physiology 1, 講師（学部内）

• 2016.10

  -

  2025.03

  School of Medicine, 生理学, 専任講師

• 2025.03

  -

  Present

  Keio University, WPI-Bio2Q

Academic Background 【 Display / hide 】

Academic Background 【 Display / hide 】

• 　

  Osaka University, 医学部

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

• 医学博士, 大阪大学医学部, Dissertation, 2001.06

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Life Science / Clinical pharmacy

• Life Science / Physiology

Research Keywords 【 Display / hide 】

Research Keywords 【 Display / hide 】

• Neuroscience

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• Development of a VHH that inhibits the binding of neuronal pentraxin 2 to a postsynaptic glutamate receptor, AMPAR

  Yokoo T., Nakakido M., Matsuda K., Caaveiro J.M.M., Fernandez-Perez J., Yuzaki M., Tsumoto K.

  Journal of Biological Chemistry 302 ( 1 )  2026.01

  ISSN  00219258

  　View Summary

  Neurons connect to each other via synapses to form neural circuits. Recent research has shown that neuropsychiatric disorders and neurological disorders, such as autism spectrum disorders and Alzheimer's disease, are synaptic diseases caused by abnormalities of synapses. Synaptic organizers are molecules responsible for synapse formation. Neuronal pentraxin 2 (NP2) is a synaptic organizer and a secreted protein that is expressed mainly in the hippocampus and cerebellum, and it contributes to synaptic plasticity. NP2 forms clusters with its family proteins, NP1 and neuronal pentraxin receptor, and binds to postsynaptic amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid–type receptors. In recent years, research has revealed the disease relevance of NP2. For example, it can be a biomarker of Alzheimer's disease, and its overexpression in the peripheral nervous system has been reported to cause chronic itch. However, the mechanism of NP2 function has not been well described at the molecular level. In this study, we developed a variable domain of a heavy-chain antibody (VHH) against NP2 to elucidate its molecular mechanism of action and to regulate its function of NP2. The obtained VHH N1 showed high specificity and affinity to NP2, and its binding mechanism was elucidated by X-ray crystallography. Furthermore, VHH N1 inhibited the binding of NP2 to amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid–type receptors, and this inhibitory activity was confirmed in cells. These results provide useful insights into the molecular mechanism of NP2 function and highlight the potential application of VHH N1 as a detection agent for NP2 or as a therapeutic agent for chronic itch.

  • Access to Document (DOI)

• Kainate receptors regulate synaptic integrity and plasticity by forming a complex with synaptic organizers in the cerebellum

  Kakegawa W., Paternain A.V., Matsuda K., Aller M.I., Iida I., Miura E., Nozawa K., Yamasaki T., Sakimura K., Yuzaki M., Lerma J.

  Cell Reports 43 ( 7 )  2024.07

  　View Summary

  Kainate (KA)-type glutamate receptors (KARs) are implicated in various neuropsychiatric and neurological disorders through their ionotropic and metabotropic actions. However, compared to AMPA- and NMDA-type receptor functions, many aspects of KAR biology remain incompletely understood. Our study demonstrates an important role of KARs in organizing climbing fiber (CF)-Purkinje cell (PC) synapses and synaptic plasticity in the cerebellum, independently of their ion channel or metabotropic functions. The amino-terminal domain (ATD) of the GluK4 KAR subunit binds to C1ql1, provided by CFs, and associates with Bai3, an adhesion-type G protein-coupled receptor expressed in PC dendrites. Mice lacking GluK4 exhibit no KAR-mediated responses, reduced C1ql1 and Bai3 levels, and fewer CF-PC synapses, along with impaired long-term depression and oculomotor learning. Remarkably, introduction of the ATD of GluK4 significantly improves all these phenotypes. These findings demonstrate that KARs act as synaptic scaffolds, orchestrating synapses by forming a KAR-C1ql1-Bai3 complex in the cerebellum.

  • Access to Document (DOI)

• C1ql1-Bai3 signaling is necessary for climbing fiber synapse formation in mature Purkinje cells in coordination with neuronal activity

  Aimi T., Matsuda K., Yuzaki M.

  Molecular Brain 16 ( 1 )  2023.12

  　View Summary

  Changes in neural activity induced by learning and novel environments have been reported to lead to the formation of new synapses in the adult brain. However, the underlying molecular mechanism is not well understood. Here, we show that Purkinje cells (PCs), which have established adult-type monosynaptic innervation by climbing fibers (CFs) after elimination of weak CFs during development, can be reinnervated by multiple CFs by increased expression of the synaptic organizer C1ql1 in CFs or Bai3, a receptor for C1ql1, in PCs. In the adult cerebellum, CFs are known to have transverse branches that run in a mediolateral direction without forming synapses with PCs. Electrophysiological, Ca2+-imaging and immunohistochemical studies showed that overexpression of C1ql1 or Bai3 caused these CF transverse branches to elongate and synapse on the distal dendrites of mature PCs. Mature PCs were also reinnervated by multiple CFs when the glutamate receptor GluD2, which is essential for the maintenance of synapses between granule cells and PCs, was deleted. Interestingly, the effect of GluD2 knockout was not observed in Bai3 knockout PCs. In addition, C1ql1 levels were significantly upregulated in CFs of GluD2 knockout mice, suggesting that endogenous, not overexpressed, C1ql1-Bai3 signaling could regulate the reinnervation of mature PCs by CFs. Furthermore, the effects of C1ql1 and Bai3 overexpression required neuronal activity in the PC and CF, respectively. C1ql1 immunoreactivity at CF-PC synapses was reduced when the neuronal activity of CFs was suppressed. These results suggest that C1ql1-Bai3 signaling may mediate CF synaptogenesis in mature PCs, potentially in concert with neuronal activity.

  • Access to Document (DOI)

• A synthetic synaptic organizer protein restores glutamatergic neuronal circuits

  Suzuki K., Elegheert J., Song I., Sasakura H., Senkov O., Matsuda K., Kakegawa W., Clayton A.J., Chang V.T., Ferrer-Ferrer M., Miura E., Kaushik R., Ikeno M., Morioka Y., Takeuchi Y., Shimada T., Otsuka S., Stoyanov S., Watanabe M., Takeuchi K., Dityatev A., Radu Aricescu A., Yuzaki M.

  Science (Science)  369 ( 6507 )  2020.08

  ISSN  00368075

  　View Summary

  Copyright © 2020 The Authors, Neuronal synapses undergo structural and functional changes throughout life, which are essential for nervous system physiology. However, these changes may also perturb the excitatory–inhibitory neurotransmission balance and trigger neuropsychiatric and neurological disorders. Molecular tools to restore this balance are highly desirable. Here, we designed and characterized CPTX, a synthetic synaptic organizer combining structural elements from cerebellin-1 and neuronal pentraxin-1. CPTX can interact with presynaptic neurexins and postsynaptic AMPA-type ionotropic glutamate receptors and induced the formation of excitatory synapses both in vitro and in vivo. CPTX restored synaptic functions, motor coordination, spatial and contextual memories, and locomotion in mouse models for cerebellar ataxia, Alzheimer’s disease, and spinal cord injury, respectively. Thus, CPTX represents a prototype for structure-guided biologics that can efficiently repair or remodel neuronal circuits.

  • Access to Document (DOI)

• Calsyntenin-3 interacts with both α- and β-neurexins in the regulation of excitatory synaptic innervation in specific Schaffer collateral pathways

  Kim H., Kim D., Kim J., Lee H.Y., Park D., Kang H., Matsuda K., Sterky F.H., Yuzaki M., Kim J.Y., Choi S.Y., Ko J., Um J.W.

  The Journal of biological chemistry (The Journal of biological chemistry)  295 ( 27 ) 9244 - 9262 2020.07

  　View Summary

  © 2020 Kim et al. Calsyntenin-3 (Clstn3) is a postsynaptic adhesion molecule that induces presynaptic differentiation via presynaptic neurexins (Nrxns), but whether Nrxns directly bind to Clstn3 has been a matter of debate. Here, using LC-MS/MS-based protein analysis, confocal microscopy, RNAscope assays, and electrophysiological recordings, we show that β-Nrxns directly interact via their LNS domain with Clstn3 and Clstn3 cadherin domains. Expression of splice site 4 (SS4) insert-positive β-Nrxn variants, but not insert-negative variants, reversed the impaired Clstn3 synaptogenic activity observed in Nrxn-deficient neurons. Consistently, Clstn3 selectively formed complexes with SS4-positive Nrxns in vivo Neuron-specific Clstn3 deletion caused significant reductions in number of excitatory synaptic inputs. Moreover, expression of Clstn3 cadherin domains in CA1 neurons of Clstn3 conditional knockout mice rescued structural deficits in excitatory synapses, especially within the stratum radiatum layer. Collectively, our results suggest that Clstn3 links to SS4-positive Nrxns to induce presynaptic differentiation and orchestrate excitatory synapse development in specific hippocampal neural circuits, including Schaffer collateral afferents.

  • Access to Document (DOI)

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Papers, etc., Registered in KOARA 【 Display / hide 】

Papers, etc., Registered in KOARA 【 Display / hide 】

• Connecting and building up specific synapses and regulating neural circuits with novel artificial proteins.

  Matsuda, Keiko

  福澤諭吉記念慶應義塾学事振興基金事業報告集 (福澤基金運営委員会)  2022

• Synaptic activity dependent extracellular Ca dynamics regulates synaptic transmission

  Matsuda, Keiko

  科学研究費補助金研究成果報告書 2021

• Construction of a novel synthetic synaptic organizer protein in excitatory and inhibitory synapses

  Matsuda, Keiko

  学事振興資金研究成果実績報告書 (慶應義塾大学)  2020

• Molecular mechanism of synapse differentiation through crosstalk of C1q family molecules and glutamate receptors

  Matsuda, Keiko

  科学研究費補助金研究成果報告書 2020

• Molecular mechanism of postsynaptic spine formation induced by synaptic differentiation via synapse organizer

  Matsuda, Keiko

  福澤諭吉記念慶應義塾学事振興基金事業報告集 (福澤基金運営委員会)  2020

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Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• Correction: Calsyntenin-3 interacts with both α- and β-neurexins in the regulation of excitatory synaptic innervation in specific schaffer collateral pathways (Journal of Biological Chemistry (2020) 295(27) (9244–9262), (S0021925817503427), (10.1074/jbc.RA120.013077))

  Kim H., Kim D., Kim J., Lee H.Y., Park D., Kang H., Matsuda K., Sterky F.H., Yuzaki M., Kim J.Y., Choi S.Y., Ko J., Um J.W.

  Journal of Biological Chemistry 300 ( 7 )  2024.07

  ISSN  00219258

  　View Summary

  An image was inadvertently reused in Figure 8D. A portion of the same image appears in both the “Nestin-Clstn3” and “+ Clstn3 Full (rescue)” panels of the “SLM” row. An incorrect image was also supplied for the “Ctrl” panel of GAD65-immunostained neurons of the SR layer in figure 9C. Corrected versions of both figures have been provided. The authors state the results and findings presented in the article remain unchanged.[Formula presented][Formula presented]

  • Access to Document (DOI)

Presentations 【 Display / hide 】

Presentations 【 Display / hide 】

• Synapse organization and modulation via C1q family proteins and their receptors

  MATSUDA KEIKO

  [Domestic presentation]  第94回日本生理学会大会, 

  2017.03

  , 

  Symposium, workshop panel (nominated)

• Synaptic organization at CA3-mossy fiber synapse through novel C1q related molecules

  MATSUDA KEIKO

  [Domestic presentation]  第39回　日本神経科学大会, 

  2016.07

  , 

  Oral presentation (general)

• Synapse organization and regulation through novel type of complement C1q family

  MATSUDA KEIKO

  [Domestic presentation]  第38回　日本神経科学大会, 

  2015.07

  , 

  Symposium, workshop panel (public)

• Cross talk between C1q family molecules and glutamate receptors in synapse formation

  MATSUDA KEIKO

  [Domestic presentation]  第36回日本神経科学会大会, 

  2013.06

  , 

  Symposium, workshop panel (nominated)

• Ｃｂｌｎ1とその関連分子群によるシナプス形成

  MATSUDA KEIKO

  [Domestic presentation]  第34回日本神経科学会大会, 

  2011.09

  , 

  Symposium, workshop panel (public)

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

Research Projects of Competitive Funds, etc. 【 Display / hide 】

• シナプス形成因子による末梢臓器ー脳連関における情報伝達分子基盤の解明

  2024.04

  -

  2027.03

  基盤研究(C), Principal investigator

• Cbln4による抑制性シナプスと興奮性シナプス分化制御機構の解明

  2021.04

  -

  2024.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

• 補体様分泌因子とグルタミン酸受容体クロストークによるシナプス成熟の分子機構解明

  2017.04

  -

  2021.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Principal investigator

• The molecular mechanism of synapse organization and modulation via C1q family proteins

  2014.04

  -

  2017.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  　View Summary

  Kainate-type ionotropic glutamate receptors (KARs) are highly expressed at synapses between mossy fibers (MFs) and CA3 pyramidal neurons in the hippocampus and important modulators of neural circuit activities. Although diverse KAR roles depend on their subcellular localization, how they are targeted to specific sites is currently unknown. We have demonstarated that the C1q-like proteins C1ql2 and C1ql3, produced by MFs, interact with the amino-terminal domains of postsynaptic GluK2 and GluK4 KAR subunits to determine location and function of KARs. In C1ql2/3-double null mice, CA3 synaptic responses lost the slow, KAR-mediated, components. Furthermore, despite induction of MF sprouting in a temporal lobe epilepsy model, KARs were not recruited to postsynaptic sites in C1ql2/3-double null mice, leading to reduced recurrent circuit activities. C1q-family proteins, broadly expressed, are likely to modulate KAR function throughout the brain.

Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• PHYSIOLOGY 1

  2026

• PHYSIOLOGY 1

  2025

• PHYSIOLOGY 1

  2024

• PHYSIOLOGY 1

  2023

• PHYSIOLOGY 1

  2022

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Courses Previously Taught 【 Display / hide 】

Courses Previously Taught 【 Display / hide 】

• 生理学Ⅰ

  Keio University

  2017.04

  -

  2018.03

  , 

  Full academic year, Laboratory work/practical work/exercise

• 生理学Ⅰ

  Keio University

  2017.04

  -

  2018.03

  , 

  Spring Semester, Lecture

• 生理学実習

  Keio University

  2015.04

  -

  2016.03

• 味覚　嗅覚

  Keio University

  2015.04

  -

  2016.03

• 聴覚

  Keio University

  2015.04

  -

  2016.03

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Memberships in Academic Societies 【 Display / hide 】

Memberships in Academic Societies 【 Display / hide 】

• Japan Neuroscience Society

  　

• Physiological Society of Japan

  　

• Society for Neuroscience