研究者詳細 - 内ヶ島　基政

論文 - 内ヶ島　基政

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Single-cell synaptome mapping of endogenous protein subpopulations in mammalian brain. 査読国際誌

Motokazu Uchigashima, Risa Iguchi, Kazuma Fujii, Kaito Shiku, Pratik Kumar, Xinyi Liu, Mari Isogai, Chiaki Hoshino, Manabu Abe, Motohiro Nozumi, Yosuke Okamura, Michihiro Igarashi, Kenji Sakimura, Ryoma Bise, Luke D Lavis, Takayasu Mikuni

Nature communications 16 ( 1 ) 9705 - 9705 2025年11月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Different spatial or temporal protein populations, such as cell-surface/intracellular or pre-existing/nascent subpopulations, determine the basal and activity-induced functions of individual synapses within a neuron in vivo. Here, we developed a simple and generalizable platform to image different spatial and temporal subpopulations of endogenous proteins at thousands of synapses in single neurons in the mammalian brain. The platform is based on the development, improvement and integration of CRISPR-Cas9-mediated protein labeling methods, chemical tag labeling techniques, and a semi-automatic analytical pipeline. The combined platform enables whole-cell mapping of total, cell-surface, intracellular, pre-existing, nascent or nascent-and-surface populations of endogenous proteins, such as receptor, scaffold and signaling proteins, at thousands of synapses in individual neurons in living or fixed mouse brain. Our single-cell "synaptome" mapping of endogenous protein subpopulations comprehensively visualizes the spatial representation of synapse diversity in protein localization, trafficking and turnover, providing valuable insights into single-cell organization and computations in the brain.

DOI： 10.1038/s41467-025-65813-w

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SeeThrough: a rationally designed skull clearing technique for in vivo brain imaging. 査読国際誌

Xinyi Liu, Motokazu Uchigashima, Ikumi Oomoto, Yoshihito Saito, Hitoshi Uchida, Shinya Oginezawa, Keiko Masuda, Daisuke Satoh, Manabu Abe, Kenji Sakimura, Yoshihiro Shimizu, Masanori Murayama, Kazuki Tainaka, Takayasu Mikuni

Nature communications 16 ( 1 ) 7584 - 7584 2025年8月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）

Light scattering in the skull limits optical access to the brain. Here we present SeeThrough, a skull-clearing technique that enables simple, high-resolution, and minimally-invasive brain imaging without skull removal. Through systematic screening of over 1600 chemicals, we rationally developed a refractive index-matching solution that combines water- and organic solvent-based components, achieving both high clearing efficiency and biocompatibility. The reagents exhibit minimal brain penetration, maintain tissue integrity, and avoid inflammatory responses. Notably, SeeThrough provides imaging sensitivity and contrast comparable to open-skull window imaging, while permitting minimally-invasive monitoring of brain border macrophages as well as blood and cerebrospinal fluid dynamics. Combined with two-photon imaging, SeeThrough enables spatially and temporally scalable imaging applications in the mouse brain, including ~400 µm deep imaging, one-month longitudinal imaging, and mesoscale, cellular-resolution monitoring of brain activity for network-level analysis. Thus, SeeThrough offers a broadly accessible platform for high-throughput, physiology-preserving imaging of the brain parenchyma and brain-skull interface.

DOI： 10.1038/s41467-025-62836-1

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Single-cell synaptome mapping: its technical basis and applications in critical period plasticity research 査読国際誌

Motokazu Uchigashima, Takayasu Mikuni

Front Neural Circuits 18 1523614 - 1523614 2024年

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Our brain adapts to the environment by optimizing its function through experience-dependent cortical plasticity. This plasticity is transiently enhanced during a developmental stage, known as the "critical period," and subsequently maintained at lower levels throughout adulthood. Thus, understanding the mechanism underlying critical period plasticity is crucial for improving brain adaptability across the lifespan. Critical period plasticity relies on activity-dependent circuit remodeling through anatomical and functional changes at individual synapses. However, it remains challenging to identify the molecular signatures of synapses responsible for critical period plasticity and to understand how these plasticity-related synapses are spatiotemporally organized within a neuron. Recent advances in genetic tools and genome editing methodologies have enabled single-cell endogenous protein labeling in the brain, allowing for comprehensive molecular profiling of individual synapses within a neuron, namely "single-cell synaptome mapping." This promising approach can facilitate insights into the spatiotemporal organization of synapses that are sparse yet functionally important within single neurons. In this review, we introduce the basics of single-cell synaptome mapping and discuss its methodologies and applications to investigate the synaptic and cellular mechanisms underlying circuit remodeling during the critical period.

DOI： 10.3389/fncir.2024.1523614

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Neuroligin-3: A Circuit-Specific Synapse Organizer That Shapes Normal Function and Autism Spectrum Disorder-Associated Dysfunction 招待査読国際誌

Motokazu Uchigashima, Amy Cheung, Kensuke Futai

Frontiers in Molecular Neuroscience 14 749164 - 749164 2021年10月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Frontiers Media SA

Chemical synapses provide a vital foundation for neuron-neuron communication and overall brain function. By tethering closely apposed molecular machinery for presynaptic neurotransmitter release and postsynaptic signal transduction, circuit- and context- specific synaptic properties can drive neuronal computations for animal behavior. Trans-synaptic signaling via synaptic cell adhesion molecules (CAMs) serves as a promising mechanism to generate the molecular diversity of chemical synapses. Neuroligins (Nlgns) were discovered as postsynaptic CAMs that can bind to presynaptic CAMs like Neurexins (Nrxns) at the synaptic cleft. Among the four (Nlgn1-4) or five (Nlgn1-3, Nlgn4X, and Nlgn4Y) isoforms in rodents or humans, respectively, Nlgn3 has a heterogeneous expression and function at particular subsets of chemical synapses and strong association with non-syndromic autism spectrum disorder (ASD). Several lines of evidence have suggested that the unique expression and function of Nlgn3 protein underlie circuit-specific dysfunction characteristic of non-syndromic ASD caused by the disruption of Nlgn3 gene. Furthermore, recent studies have uncovered the molecular mechanism underlying input cell-dependent expression of Nlgn3 protein at hippocampal inhibitory synapses, in which trans-synaptic signaling of specific alternatively spliced isoforms of Nlgn3 and Nrxn plays a critical role. In this review article, we overview the molecular, anatomical, and physiological knowledge about Nlgn3, focusing on the circuit-specific function of mammalian Nlgn3 and its underlying molecular mechanism. This will provide not only new insight into specific Nlgn3-mediated trans-synaptic interactions as molecular codes for synapse specification but also a better understanding of the pathophysiological basis for non-syndromic ASD associated with functional impairment in Nlgn3 gene.

DOI： 10.3389/fnmol.2021.749164

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Specific Neuroligin3-αNeurexin1 signaling regulates GABAergic synaptic function in mouse hippocampus. 査読国際誌

Motokazu Uchigashima, Kohtarou Konno, Emily Demchak, Amy Cheung, Takuya Watanabe, David G Keener, Manabu Abe, Timmy Le, Kenji Sakimura, Toshikuni Sasaoka, Takeshi Uemura, Yuka Imamura Kawasawa, Masahiko Watanabe, Kensuke Futai

eLife 9 2020年12月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）

Synapse formation and regulation require signaling interactions between pre- and postsynaptic proteins, notably cell adhesion molecules (CAMs). It has been proposed that the functions of neuroligins (Nlgns), postsynaptic CAMs, rely on the formation of trans-synaptic complexes with neurexins (Nrxns), presynaptic CAMs. Nlgn3 is a unique Nlgn isoform that localizes at both excitatory and inhibitory synapses. However, Nlgn3 function mediated via Nrxn interactions is unknown. Here we demonstrate that Nlgn3 localizes at postsynaptic sites apposing vesicular glutamate transporter 3-expressing (VGT3+) inhibitory terminals and regulates VGT3+ inhibitory interneuron-mediated synaptic transmission in mouse organotypic slice cultures. Gene expression analysis of interneurons revealed that the αNrxn1+AS4 splice isoform is highly expressed in VGT3+ interneurons as compared with other interneurons. Most importantly, postsynaptic Nlgn3 requires presynaptic αNrxn1+AS4 expressed in VGT3+ interneurons to regulate inhibitory synaptic transmission. Our results indicate that specific Nlgn-Nrxn signaling generates distinct functional properties at synapses.

DOI： 10.7554/eLife.59545

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Differential expression of neurexin genes in the mouse brain. 査読国際誌

Motokazu Uchigashima, Amy Cheung, Julie Suh, Masahiko Watanabe, Kensuke Futai

The Journal of comparative neurology 527 ( 12 ) 1940 - 1965 2019年8月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Synapses, highly specialized membrane junctions between neurons, connect presynaptic neurotransmitter release sites and postsynaptic ligand-gated channels. Neurexins (Nrxns), a family of presynaptic adhesion molecules, have been characterized as major regulators of synapse development and function. Via their extracellular domains, Nrxns bind to different postsynaptic proteins, generating highly diverse functional readouts through their postsynaptic binding partners. Not surprisingly given these versatile protein interactions, mutations and deletions of Nrxn genes have been identified in patients with autism spectrum disorders, intellectual disabilities, and schizophrenia. Therefore, elucidating the expression profiles of Nrxns in the brain is of high significance. Here, using chromogenic and fluorescent in situ hybridization, we characterize the expression patterns of Nrxn isoforms throughout the brain. We found that each Nrxn isoform displays a unique expression profile in a region-, cell type-, and sensory system-specific manner. Interestingly, we also found that αNrxn1 and αNrxn2 mRNAs are expressed in non-neuronal cells, including astrocytes and oligodendrocytes. Lastly, we found diverse expression patterns of genes that encode Nrxn binding proteins, such as Neuroligins (Nlgns), Leucine-rich repeat transmembrane neuronal protein (Lrrtms) and Latrophilins (Adgrls), suggesting that Nrxn proteins can mediate numerous combinations of trans-synaptic interactions. Together, our anatomical profiling of Nrxn gene expression reflects the diverse roles of Nrxn molecules.

DOI： 10.1002/cne.24664

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Dopamine synapse is a neuroligin-2-mediated contact between dopaminergic presynaptic and GABAergic postsynaptic structures 査読

Motokazu Uchigashima, Toshihisa Ohtsuka, Kazuto Kobayashi, Masahiko Watanabe

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 113 ( 15 ) 4206 - 4211 2016年4月

Single-cell endogenous protein labeling via CRISPR-Cas9-mediated genome editing in the mouse brain. 招待査読

Motokazu Uchigashima, Takayasu Mikuni

Anatomical science international 100 ( 4 ) 579 - 590 2025年7月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

High-precision mapping of endogenous proteins is essential for understanding the molecular mechanism underlying neuronal functions in the brain. The SLENDR (single-cell labeling of endogenous proteins by clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-mediated homology-directed repair) technique provides single-cell endogenous protein labeling with genetically encoded tags within the mammalian brain through precise genome editing via homology-directed repair (HDR). This technique is based on the introduction of HDR-mediated genome editing into neuronal progenitors in embryonic brains by in utero electroporation. Subsequent histological analyses enable high-resolution interrogation of the subcellular distribution of endogenous proteins within a single neuron using conventional fluorescent microscopy. Here, we describe a step-by-step protocol for the SLENDR technique to label endogenous proteins with genetically encoded tags in single pyramidal cells of the mouse primary somatosensory cortex. This protocol would be helpful to visualize the molecular organization underlying biological processes at single-neuron levels in the brain, such as signal processing from synaptic inputs to neuronal outputs across different scales.

DOI： 10.1007/s12565-025-00866-x

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Regulation of Presynaptic Release Machinery by Cell Adhesion Molecules 国際誌

Motokazu Uchigashima, Yasunori Hayashi, Kensuke Futai

Advances in Neurobiology 33 333 - 356 2023年

General Design Strategy to Precisely Control the Emission of Fluorophores via a Twisted Intramolecular Charge Transfer (TICT) Process. 査読国際誌

Kenjiro Hanaoka, Shimpei Iwaki, Kiyoshi Yagi, Takuya Myochin, Takayuki Ikeno, Hisashi Ohno, Eita Sasaki, Toru Komatsu, Tasuku Ueno, Motokazu Uchigashima, Takayasu Mikuni, Kazuki Tainaka, Shinya Tahara, Satoshi Takeuchi, Tahei Tahara, Masanobu Uchiyama, Tetsuo Nagano, Yasuteru Urano

Journal of the American Chemical Society 144 ( 43 ) 19778 - 19790 2022年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Fluorogenic probes for bioimaging have become essential tools for life science and medicine, and the key to their development is a precise understanding of the mechanisms available for fluorescence off/on control, such as photoinduced electron transfer (PeT) and Förster resonance energy transfer (FRET). Here we establish a new molecular design strategy to rationally develop activatable fluorescent probes, which exhibit a fluorescence off/on change in response to target biomolecules, by controlling the twisted intramolecular charge transfer (TICT) process. This approach was developed on the basis of a thorough investigation of the fluorescence quenching mechanism of N-phenyl rhodamine dyes (commercially available as the QSY series) by means of time-dependent density functional theory (TD-DFT) calculations and photophysical evaluation of their derivatives. To illustrate and validate this TICT-based design strategy, we employed it to develop practical fluorogenic probes for HaloTag and SNAP-tag. We further show that the TICT-controlled fluorescence off/on mechanism is generalizable by synthesizing a Si-rhodamine-based fluorogenic probe for HaloTag, thus providing a palette of chemical dyes that spans the visible and near-infrared range.

DOI： 10.1021/jacs.2c06397

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Enhanced Retrieval of Taste Associative Memory by Chemogenetic Activation of Locus Coeruleus Norepinephrine Neurons. 査読国際誌

Ryoji Fukabori, Yoshio Iguchi, Shigeki Kato, Kazumi Takahashi, Satoshi Eifuku, Shingo Tsuji, Akihiro Hazama, Motokazu Uchigashima, Masahiko Watanabe, Hiroshi Mizuma, Yilong Cui, Hirotaka Onoe, Keigo Hikishima, Yasunobu Yasoshima, Makoto Osanai, Ryo Inagaki, Kohji Fukunaga, Takuma Nishijo, Toshihiko Momiyama, Richard Benton, Kazuto Kobayashi

The Journal of neuroscience : the official journal of the Society for Neuroscience 40 ( 43 ) 8367 - 8385 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

The ability of animals to retrieve memories stored in response to the environment is essential for behavioral adaptation. Norepinephrine (NE)-containing neurons in the brain play a key role in the modulation of synaptic plasticity underlying various processes of memory formation. However, the role of the central NE system in memory retrieval remains unclear. Here, we developed a novel chemogenetic activation strategy exploiting insect olfactory ionotropic receptors (IRs), termed "IR-mediated neuronal activation," and used it for selective stimulation of NE neurons in the locus coeruleus (LC). Drosophila melanogaster IR84a and IR8a subunits were expressed in LC NE neurons in transgenic mice. Application of phenylacetic acid (a specific ligand for the IR84a/IR8a complex) at appropriate doses induced excitatory responses of NE neurons expressing the receptors in both slice preparations and in vivo electrophysiological conditions, resulting in a marked increase of NE release in the LC nerve terminal regions (male and female). Ligand-induced activation of LC NE neurons enhanced the retrieval process of conditioned taste aversion without affecting taste sensitivity, general arousal state, and locomotor activity. This enhancing effect on taste memory retrieval was mediated, in part, through α1- and β-adrenergic receptors in the basolateral nucleus of the amygdala (BLA; male). Pharmacological inhibition of LC NE neurons confirmed the facilitative role of these neurons in memory retrieval via adrenergic receptors in the BLA (male). Our findings indicate that the LC NE system, through projections to the BLA, controls the retrieval process of taste associative memory.SIGNIFICANCE STATEMENT Norepinephrine (NE)-containing neurons in the brain play a key role in the modulation of synaptic plasticity underlying various processes of memory formation, but the role of the NE system in memory retrieval remains unclear. We developed a chemogenetic activation system based on insect olfactory ionotropic receptors and used it for selective stimulation of NE neurons in the locus coeruleus (LC) in transgenic mice. Ligand-induced activation of LC NE neurons enhanced the retrieval of conditioned taste aversion, which was mediated, in part, through adrenoceptors in the basolateral amygdala. Pharmacological blockade of LC activity confirmed the facilitative role of these neurons in memory retrieval. Our findings indicate that the LC-amygdala pathway plays an important role in the recall of taste associative memory.

DOI： 10.1523/JNEUROSCI.1720-20.2020

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Neuroligin3 splice isoforms shape inhibitory synaptic function in the mouse hippocampus. 査読国際誌

Motokazu Uchigashima, Ming Leung, Takuya Watanabe, Amy Cheung, Timmy Le, Sabine Pallat, Alexandre Luis Marques Dinis, Masahiko Watanabe, Yuka Imamura Kawasawa, Kensuke Futai

The Journal of biological chemistry 295 ( 25 ) 8589 - 8595 2020年6月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）

Synapse formation is a dynamic process essential for the development and maturation of the neuronal circuitry in the brain. At the synaptic cleft, trans-synaptic protein-protein interactions are major biological determinants of proper synapse efficacy. The balance of excitatory and inhibitory synaptic transmission (E-I balance) stabilizes synaptic activity, and dysregulation of the E-I balance has been implicated in neurodevelopmental disorders, including autism spectrum disorders. However, the molecular mechanisms underlying the E-I balance remain to be elucidated. Here, using single-cell transcriptomics, immunohistochemistry, and electrophysiology approaches to murine CA1 pyramidal neurons obtained from organotypic hippocampal slice cultures, we investigate neuroligin (Nlgn) genes that encode a family of postsynaptic adhesion molecules known to shape excitatory and inhibitory synaptic function. We demonstrate that the NLGN3 protein differentially regulates inhibitory synaptic transmission in a splice isoform-dependent manner at hippocampal CA1 synapses. We also found that distinct subcellular localizations of the NLGN3 isoforms contribute to the functional differences observed among these isoforms. Finally, results from single-cell RNA-Seq analyses revealed that Nlgn1 and Nlgn3 are the major murine Nlgn genes and that the expression levels of the Nlgn splice isoforms are highly diverse in CA1 pyramidal neurons. Our results delineate isoform-specific effects of Nlgn genes on the E-I balance in the murine hippocampus.

DOI： 10.1074/jbc.AC120.012571

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Methodological approaches to understand the molecular mechanism of structural plasticity of dendritic spines. 招待国際誌

Takayasu Mikuni, Motokazu Uchigashima

The European journal of neuroscience 54 ( 8 ) 6902 - 6911 2020年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Dendritic spines are tiny protrusions emanating from the neuronal dendrites, typically housing single excitatory postsynapses. Structural plasticity of dendritic spines is considered to be essential for synaptic functional plasticity and also reorganization of neural circuits during learning and memory. Structural plasticity of spines is mediated by complex biochemical signaling with various spatial and temporal scales. A variety of methods based on pharmacological, genetic, molecular, imaging and optical approaches has been developed and applied to dissect the complex signal transduction pathways. In this review, we overview both conventional and new methodological approaches to identify, monitor and manipulate key molecules for structural plasticity of dendritic spines, ultimately aiming to understand the molecular mechanism of learning and memory in behaving animals.

DOI： 10.1111/ejn.14734

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Endocannabinoid and nitric oxide systems of the hypothalamic paraventricular nucleus mediate effects of NPY on energy expenditure. 査読国際誌

Zoltán Péterfi, Imre Farkas, Raphael G P Denis, Erzsébet Farkas, Motokazu Uchigashima, Tamás Füzesi, Masahiko Watanabe, Ronald M Lechan, Zsolt Liposits, Serge Luquet, Csaba Fekete

Molecular metabolism 18 120 - 133 2018年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: Neuropeptide Y (NPY) is one of the most potent orexigenic peptides. The hypothalamic paraventricular nucleus (PVN) is a major locus where NPY exerts its effects on energy homeostasis. We investigated how NPY exerts its effect within the PVN. METHODS: Patch clamp electrophysiology and Ca2+ imaging were used to understand the involvement of Ca2+ signaling and retrograde transmitter systems in the mediation of NPY induced effects in the PVN. Immuno-electron microscopy were performed to elucidate the subcellular localization of the elements of nitric oxide (NO) system in the parvocellular PVN. In vivo metabolic profiling was performed to understand the role of the endocannabinoid and NO systems of the PVN in the mediation of NPY induced changes of energy homeostasis. RESULTS: We demonstrated that NPY inhibits synaptic inputs of parvocellular neurons in the PVN by activating endocannabinoid and NO retrograde transmitter systems via mobilization of Ca2+ from the endoplasmic reticulum, suggesting that NPY gates the synaptic inputs of parvocellular neurons in the PVN to prevent the influence of non-feeding-related inputs. While intraPVN administered NPY regulates food intake and locomotor activity via NO signaling, the endocannabinoid system of the PVN selectively mediates NPY-induced decrease in energy expenditure. CONCLUSION: Thus, within the PVN, NPY stimulates the release of endocannabinoids and NO via Ca2+-influx from the endoplasmic reticulum. Both transmitter systems appear to have unique roles in the mediation of the NPY-induced regulation of energy homeostasis, suggesting that NPY regulates food intake, energy expenditure, and locomotor activity through different neuronal networks of this nucleus.

DOI： 10.1016/j.molmet.2018.08.007

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Monitoring and Updating of Action Selection for Goal-Directed Behavior through the Striatal Direct and Indirect Pathways. 査読国際誌

Satoshi Nonomura, Kayo Nishizawa, Yutaka Sakai, Yasuo Kawaguchi, Shigeki Kato, Motokazu Uchigashima, Masahiko Watanabe, Ko Yamanaka, Kazuki Enomoto, Satomi Chiken, Hiromi Sano, Shogo Soma, Junichi Yoshida, Kazuyuki Samejima, Masaaki Ogawa, Kazuto Kobayashi, Atsushi Nambu, Yoshikazu Isomura, Minoru Kimura

Neuron 99 ( 6 ) 1302 - 1314 2018年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

The basal ganglia play key roles in adaptive behaviors guided by reward and punishment. However, despite accumulating knowledge, few studies have tested how heterogeneous signals in the basal ganglia are organized and coordinated for goal-directed behavior. In this study, we investigated neuronal signals of the direct and indirect pathways of the basal ganglia as rats performed a lever push/pull task for a probabilistic reward. In the dorsomedial striatum, we found that optogenetically and electrophysiologically identified direct pathway neurons encoded reward outcomes, whereas indirect pathway neurons encoded no-reward outcome and next-action selection. Outcome coding occurred in association with the chosen action. In support of pathway-specific neuronal coding, light activation induced a bias on repeat selection of the same action in the direct pathway, but on switch selection in the indirect pathway. Our data reveal the mechanisms underlying monitoring and updating of action selection for goal-directed behavior through basal ganglia circuits.

DOI： 10.1016/j.neuron.2018.08.002

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Activity-Induced Regulation of Synaptic Strength through the Chromatin Reader L3mbtl1 査読

Wenjie Mao, Anna C. Salzberg, Motokazu Uchigashima, Yuto Hasegawa, Hanno Hock, Masahiko Watanabe, Schahram Akbarian, Yuka Imamura Kawasawa, Kensuke Futai

Cell Reports 23 ( 11 ) 3209 - 3222 2018年6月

Endocytosis following dopamine D2 receptor activation is critical for neuronal activity and dendritic spine formation via Rabex-5/PDGFRβ signaling in striatopallidal medium spiny neurons. 査読

Shioda N, Yabuki Y, Wang Y, Uchigashima M, Hikida T, Sasaoka T, Mori H, Watanabe M, Sasahara M, Fukunaga K

Mol Psychiatry 22 ( 8 ) 1205 - 1222 2017年8月

LUsing a novel PV-Cre rat model to characterize pallidonigral cells and their terminations 査読

Yoon-Mi Oh, Fuyuki Karube, Susumu Takahashi, Kenta Kobayashi, Masahiko Takada, Motokazu Uchigashima, Masahiko Watanabe, Kayo Nishizawa, Kazuto Kobayashi, Fumino Fujiyama

BRAIN STRUCTURE & FUNCTION 222 ( 5 ) 2359 - 2378 2017年7月

Ventrolateral Striatal Medium Spiny Neurons Positively Regulate Food-Incentive, Goal-Directed Behavior Independently of D1 and D2 Selectivity 査読

Akiyo Natsubori, Iku Tsutsui-Kimura, Hiroshi Nishida, Youcef Bouchekioua, Hiroshi Sekiya, Motokazu Uchigashima, Masahiko Watanabe, Alban de Kerchove d'Exaerde, Masaru Mimura, Norio Takata, Kenji F. Tanaka

JOURNAL OF NEUROSCIENCE 37 ( 10 ) 2723 - 2733 2017年3月

Dysfunction of ventrolateral striatal dopamine receptor type 2-expressing medium spiny neurons impairs instrumental motivation 査読

Iku Tsutsui-Kimura, Hiroyuki Takiue, Keitaro Yoshida, Ming Xu, Ryutaro Yano, Hiroyuki Ohta, Hiroshi Nishida, Youcef Bouchekioua, Hideyuki Okano, Motokazu Uchigashima, Masahiko Watanabe, Norio Takata, Michael R. Drew, Hiromi Sano, Masaru Mimura, Kenji F. Tanaka

Nature Communications 8 14304 2017年2月

The Metabotropic Glutamate Receptor Subtype 1 Mediates Experience-Dependent Maintenance of Mature Synaptic Connectivity in the Visual Thalamus 査読

Madoka Narushima, Motokazu Uchigashima, Yuki Yagasaki, Takeshi Harada, Yasuyuki Nagumo, Naofumi Uesaka, Kouichi Hashimoto, Atsu Aiba, Masahiko Watanabe, Mariko Miyata, Masanobu Kano

NEURON 91 ( 5 ) 1097 - 1109 2016年9月

Crucial Roles of the Endocannabinoid 2-Arachidonoylglycerol in the Suppression of Epileptic Seizures 査読

Yuki Sugaya, Maya Yamazaki, Motokazu Uchigashima, Kenta Kobayashi, Masahiko Watanabe, Kenji Sakimura, Masanobu Kano

CELL REPORTS 16 ( 5 ) 1405 - 1415 2016年8月

Transsynaptic Modulation of Kainate Receptor Functions by C1q-like Proteins 査読

Keiko Matsuda, Timotheus Budisantoso, Nikolaos Mitakidis, Yuki Sugaya, Eriko Miura, Wataru Kakegawa, Miwako Yamasaki, Kohtarou Konno, Motokazu Uchigashima, Manabu Abe, Izumi Watanabe, Masanobu Kano, Masahiko Watanabe, Kenji Sakimura, A. Radu Aricescu, Michisuke Yuzaki

NEURON 90 ( 4 ) 752 - 767 2016年5月

Territories of heterologous inputs onto Purkinje cell dendrites are segregated by mGluR1-dependent parallel fiber synapse elimination 査読

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 2016年2月

Phosphoproteomics of the Dopamine Pathway Enables Discovery of Rap1 Activation as a Reward Signal In Vivo 査読

Taku Nagai, Shinichi Nakamuta, Keisuke Kuroda, Sakura Nakauchi, Tomoki Nishioka, Tetsuya Takano, Xinjian Zhang, Daisuke Tsuboi, Yasuhiro Funahashi, Takashi Nakano, Junichiro Yoshimoto, Kenta Kobayashi, Motokazu Uchigashima, Masahiko Watanabe, Masami Miura, Akinori Nishi, Kazuto Kobayashi, Kiyofumi Yamada, Mutsuki Amano, Kozo Kaibuchi

NEURON 89 ( 3 ) 550 - 565 2016年2月

Production of monoclonal antibodies against GPCR using cell-free synthesized GPCR antigen and biotinylated liposome-based interaction assay 査読

Hiroyuki Takeda, Tomio Ogasawara, Tatsuhiko Ozawa, Atsushi Muraguchi, Pei-Ju Jih, Ryo Morishita, Motokazu Uchigashima, Masahiko Watanabe, Toyoshi Fujimoto, Takahiro Iwasaki, Yaeta Endo, Tatsuya Sawasaki

SCIENTIFIC REPORTS 5 11333 2015年6月

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 査読

Yuki Omiya, Motokazu Uchigashima, Kohtarou Konno, Miwako Yamasaki, Taisuke Miyazaki, Takayuki Yoshida, Ichiro Kusumi, Masahiko Watanabe

JOURNAL OF NEUROSCIENCE 35 ( 10 ) 4215 - 4228 2015年3月

Cellular and subcellular localization of cholecystokinin (CCK)-1 receptors in the pancreas, gallbladder, and stomach of mice 査読

Kohtarou Konno, Hiromi Takahashi-Iwanaga, Motokazu Uchigashima, Kyoko Miyasaka, Akihiro Funakoshi, Masahiko Watanabe, Toshihiko Iwanaga

HISTOCHEMISTRY AND CELL BIOLOGY 143 ( 3 ) 301 - 312 2015年3月

Retrograde Signaling for Climbing Fiber Synapse Elimination 査読

Naofumi Uesaka, Motokazu Uchigashima, Takayasu Mikuni, Hirokazu Hirai, Masahiko Watanabe, Masanobu Kano

CEREBELLUM 14 ( 1 ) 4 - 7 2015年2月

Neuron type- and input pathway-dependent expression of Slc4a10 in adult mouse brains 査読

Xiaohong Song, Miwako Yamasaki, Taisuke Miyazaki, Kohtarou Konno, Motokazu Uchigashima, Masahiko Watanabe

EUROPEAN JOURNAL OF NEUROSCIENCE 40 ( 5 ) 2797 - 2810 2014年9月

GABAergic neurons in the ventral tegmental area receive dual GABA/enkephalin-mediated inhibitory inputs from the bed nucleus of the stria terminalis 査読

Takehiro Kudo, Kohtarou Konno, Motokazu Uchigashima, Yuchio Yanagawa, Ichiro Sora, Masabumi Minami, Masahiko Watanabe

EUROPEAN JOURNAL OF NEUROSCIENCE 39 ( 11 ) 1796 - 1809 2014年6月

Retrograde semaphorin signaling regulates synapse elimination in the developing mouse brain 査読

Naofumi Uesaka, Motokazu Uchigashima, Takayasu Mikuni, Takanobu Nakazawa, Harumi Nakao, Hirokazu Hirai, Atsu Aiba, Masahiko Watanabe, Masanobu Kano

SCIENCE 344 ( 6187 ) 1020 - 1023 2014年5月

Enriched Expression of GluD1 in Higher Brain Regions and Its Involvement in Parallel Fiber-Interneuron Synapse Formation in the Cerebellum 査読

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 2014年5月

Chronic Alterations in Monoaminergic Cells in the Locus Coeruleus in Orexin Neuron-Ablated Narcoleptic Mice 査読

Natsuko Tsujino, Tomomi Tsunematsu, Motokazu Uchigashima, Kohtarou Konno, Akihiro Yamanaka, Kazuto Kobayashi, Masahiko Watanabe, Yoshimasa Koyama, Takeshi Sakurai

PLOS ONE 8 ( 7 ) e70012 2013年7月

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 査読

Issei Kawakita, Motokazu Uchigashima, Kohtarou Konno, Taisuke Miyazaki, Miwako Yamasaki, Masahiko Watanabe

EUROPEAN JOURNAL OF NEUROSCIENCE 37 ( 4 ) 532 - 543 2013年2月

Three Types of Neurochemical Projection from the Bed Nucleus of the Stria Terminalis to the Ventral Tegmental Area in Adult Mice 査読

Takehiro Kudo, Motokazu Uchigashima, Taisuke Miyazaki, Kohtarou Konno, Miwako Yamasaki, Yuchio Yanagawa, Masabumi Minami, Masahiko Watanabe

JOURNAL OF NEUROSCIENCE 32 ( 50 ) 18035 - 18046 2012年12月

Striatal Indirect Pathway Contributes to Selection Accuracy of Learned Motor Actions 査読

Kayo Nishizawa, Ryoji Fukabori, Kana Okada, Nobuyuki Kai, Motokazu Uchigashima, Masahiko Watanabe, Akira Shiota, Masatsugu Ueda, Yuji Tsutsui, Kazuto Kobayashi

JOURNAL OF NEUROSCIENCE 32 ( 39 ) 13421 - 13432 2012年9月

Localization of Acetylcholine-Related Molecules in the Retina: Implication of the Communication from Photoreceptor to Retinal Pigment Epithelium 査読

Hidetaka Matsumoto, Koji Shibasaki, Motokazu Uchigashima, Amane Koizumi, Masashi Kurachi, Yasuhiro Moriwaki, Hidemi Misawa, Koichiro Kawashima, Masahiko Watanabe, Shoji Kishi, Yasuki Ishizaki

PLOS ONE 7 ( 8 ) e42841 2012年8月

Synapse type-independent degradation of the endocannabinoid 2-arachidonoylglycerol after retrograde synaptic suppression 査読

Asami Tanimura, Motokazu Uchigashima, Maya Yamazaki, Naofumi Uesaka, Takayasu Mikuni, Manabu Abe, Kouichi Hashimoto, Masahiko Watanabe, Kenji Sakimura, Masanobu Kano

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 109 ( 30 ) 12195 - 12200 2012年7月

Lack of Molecular-Anatomical Evidence for GABAergic Influence on Axon Initial Segment of Cerebellar Purkinje Cells by the Pinceau Formation 査読

Atsushi Iwakura, Motokazu Uchigashima, Taisuke Miyazaki, Miwako Yamasaki, Masahiko Watanabe

JOURNAL OF NEUROSCIENCE 32 ( 27 ) 9438 - 9448 2012年7月

TRIM67 Protein Negatively Regulates Ras Activity through Degradation of 80K-H and Induces Neuritogenesis 査読

Hiroaki Yaguchi, Fumihiko Okumura, Hidehisa Takahashi, Takahiro Kano, Hiroyuki Kameda, Motokazu Uchigashima, Shinya Tanaka, Masahiko Watanabe, Hidenao Sasaki, Shigetsugu Hatakeyama

JOURNAL OF BIOLOGICAL CHEMISTRY 287 ( 15 ) 12050 - 12059 2012年4月

Striatal direct pathway modulates response time in execution of visual discrimination 査読

Ryoji Fukabori, Kana Okada, Kayo Nishizawa, Nobuyuki Kai, Kenta Kobayashi, Motokazu Uchigashima, Masahiko Watanabe, Yuji Tsutsui, Kazuto Kobayashi

EUROPEAN JOURNAL OF NEUROSCIENCE 35 ( 5 ) 784 - 797 2012年3月

Unbalance of CB1 receptors expressed in GABAergic and glutamatergic neurons in a transgenic mouse model of Huntington's disease 査読

Valentina Chiodi, Motokazu Uchigashima, Sarah Beggiato, Antonella Ferrante, Monica Armida, Alberto Martire, Rosa Luisa Potenza, Luca Ferraro, Sergio Tanganelli, Masahiko Watanabe, Maria Rosaria Domenici, Patrizia Popoli

NEUROBIOLOGY OF DISEASE 45 ( 3 ) 983 - 991 2012年3月

Selective Neural Pathway Targeting Reveals Key Roles of Thalamostriatal Projection in the Control of Visual Discrimination 査読

Shigeki Kato, Masahito Kuramochi, Kenta Kobayashi, Ryoji Fukabori, Kana Okada, Motokazu Uchigashima, Masahiko Watanabe, Yuji Tsutsui, Kazuto Kobayashi

JOURNAL OF NEUROSCIENCE 31 ( 47 ) 17169 - 17179 2011年11月

Molecular and morphological configuration for 2-arachidonoylglycerol-mediated retrograde signaling at mossy cell-granule cell synapses in the dentate gyrus. 査読

Uchigashima M, Yamazaki M, Yamasaki M, Tanimura A, Sakimura K, Kano M, Watanabe M

The Journal of neuroscience : the official journal of the Society for Neuroscience 31 ( 21 ) 7700 - 7714 2011年5月

担当区分：筆頭著者記述言語：英語出版者・発行元：21

2-Arachidonoylglycerol (2-AG) is the endocannabinoid that mediates retrograde suppression of neurotransmission in the brain. In the present study, we investigated the 2-AG signaling system at mossy cell (MC)-granule cell (GC) synapses in the mouse dentate gyrus, an excitatory recurrent circuit where endocannabinoids are thought to suppress epileptogenesis. First, we showed by electrophysiology that 2-AG produced by diacylglycerol lipase α(DGLα) mediated both depolarization-induced suppression of excitation and its enhancement by group I metabotropic glutamate receptor activation at MC-GC synapses, as they were abolished in DGLα-knock-out mice. Immunohistochemistry revealed that DGLα was enriched in the neck portion of GC spines forming synapses with MC terminals, whereas cannabinoid CB1 receptors accumulated in the terminal portion of MC axons. On the other hand, the major 2-AG-degrading enzyme, monoacylglycerol lipase (MGL), was absent at MC-GC synapses but was expressed in astrocytes and some inhibitory terminals. Serial electron microscopy clarified that a given GC spine was innervated by a single MC terminal and also contacted nonsynaptically by other MC terminals making synapses with other GC spines in the neighborhood. MGL-expressing elements, however, poorly covered GC spines, amounting to 17% of the total surface of GC spines by astrocytes and 4% by inhibitory terminals. Our findings provide a basis for 2-AG-mediated retrograde suppression of MC-GC synaptic transmission and also suggest that 2-AG released from activated GC spines is readily accessible to nearby MC-GC synapses by escaping from enzymatic degradation. This molecular-anatomical configuration will contribute to adjust network activity in the dentate gyrus after enhanced excitation.

DOI： 10.1523/JNEUROSCI.5665-10.2011

PubMed

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Unique inhibitory synapse with particularly rich endocannabinoid signaling machinery on pyramidal neurons in basal amygdaloid nucleus 査読

Takayuki Yoshida, Motokazu Uchigashima, Miwako Yamasaki, Istvan Katona, Maya Yamazaki, Kenji Sakimura, Masanobu Kano, Mitsuhiro Yoshioka, Masahiko Watanabe

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 108 ( 7 ) 3059 - 3064 2011年2月

Rho/Rho-kinase signaling pathway controls axon patterning of a specified subset of cranial motor neurons 査読

Kenta Kobayashi, Tomoyuki Masuda, Masanori Takahashi, Jun-ichi Miyazaki, Masahiro Nakagawa, Motokazu Uchigashima, Masahiko Watanabe, Hiroyuki Yaginuma, Noriko Osumi, Kozo Kaibuchi, Kazuto Kobayashi

EUROPEAN JOURNAL OF NEUROSCIENCE 33 ( 4 ) 612 - 621 2011年2月

Cellular expression and subcellular localization of secretogranin II in the mouse hippocampus and cerebellum 査読

Taisuke Miyazaki, Miwako Yamasaki, Motokazu Uchigashima, Ayano Matsushima, Masahiko Watanabe

EUROPEAN JOURNAL OF NEUROSCIENCE 33 ( 1 ) 82 - 94 2011年1月

Invaginating inhibitory synapse with particularly rich endocannabinoid signaling machinery in the basal nucleus of the amygdala 査読

Yoshida Takayuki, Uchigashima Motokazu, Yamasaki Miwako, Katona Istvan, Yamazaki Maya, Sakimura Kenji, Kano Masanobu, Yoshioka Mitsuhiro, Watanabe Masahiko

NEUROSCIENCE RESEARCH 71 E93 - E94 2011年

Neurochemical characterization of neurons in the bed nucleus of the stria terminalis projecting to the ventral tegmental area 査読

Kudo Takehiro, Uchigashima Motokazu, Miyazaki Taisuke, Yamasaki Miwako, Minami Masabumi, Watanabe Masahiko

NEUROSCIENCE RESEARCH 71 E322 2011年

Cytochemical and cytological properties of perineuronal oligodendrocytes in the mouse cortex 査読

Chihiro Takasaki, Miwako Yamasaki, Motokazu Uchigashima, Kohtarou Konno, Yuchio Yanagawa, Masahiko Watanabe

European Journal of Neuroscience 32 ( 8 ) 1326 - 1336 2010年10月

The Endocannabinoid 2-Arachidonoylglycerol Produced by Diacylglycerol Lipase alpha Mediates Retrograde Suppression of Synaptic Transmission 査読

Asami Tanimura, Maya Yamazaki, Yuki Hashimotodani, Motokazu Uchigashima, Shinya Kawata, Manabu Abe, Yoshihiro Kita, Kouichi Hashimoto, Takao Shimizu, Masahiko Watanabe, Kenji Sakimura, Masanobu Kano

NEURON 65 ( 3 ) 320 - 327 2010年2月

Endocannabinoid-Mediated Control of Synaptic Transmission 査読

Masanobu Kano, Takako Ohno-Shosaku, Yuki Hashimotodani, Motokazu Uchigashima, Masahiko Watanabe

PHYSIOLOGICAL REVIEWS 89 ( 1 ) 309 - 380 2009年1月

Key Modulatory Role of Presynaptic Adenosine A(2A) Receptors in Cortical Neurotransmission to the Striatal Direct Pathway 査読

Cesar Quiroz, Rafael Lujan, Motokazu Uchigashima, Ana Patricia Simoes, Talia N. Lerner, Janusz Borycz, Anil Kachroo, Paula M. Canas, Marco Orru, Michael A. Schwarzschild, Diane L. Rosin, Anatol C. Kreitzer, Rodrigo A. Cunha, Masahiko Watanabe, Sergi Ferre

THESCIENTIFICWORLDJOURNAL 9 1321 - 1344 2009年

Predominant expression of phospholipase C beta 1 in telencephalic principal neurons and cerebellar interneurons, and its close association with related signaling molecules in somatodendritic neuronal elements 査読

Masahiro Fukaya, Motokazu Uchigashima, Sachi Nomura, Yuta Hasegawa, Hisaya Kikuchi, Masahiko Watanabe

EUROPEAN JOURNAL OF NEUROSCIENCE 28 ( 9 ) 1744 - 1759 2008年11月

Evidence against GABA release from glutamatergic mossy fiber terminals in the developing hippocampus 査読

Motokazu Uchigashima, Masahiro Fukaya, Masahiko Watanabe, Haruyuki Kamiya

JOURNAL OF NEUROSCIENCE 27 ( 30 ) 8088 - 8100 2007年7月

Subcellular arrangement of molecules for 2-arachidonoyl-glycerol-mediated retrograde signaling and its physiological contribution to synaptic modulation in the striatum 査読

Motokazu Uchigashima, Madoka Narushima, Masahiro Fukaya, Istvan Katona, Masanobu Kano, Masahiko Watanabe

JOURNAL OF NEUROSCIENCE 27 ( 14 ) 3663 - 3676 2007年4月

Tonic enhancement of endocannabinoid-mediated retrograde suppression of inhibition by cholinergic interneuron activity in the striatum 査読

Madoka Narushima, Motokazu Uchigashima, Masahiro Fukaya, Minoru Matsui, Toshiya Manabe, Kouichi Hashimoto, Masahiko Watanabe, Masanobu Kano

JOURNAL OF NEUROSCIENCE 27 ( 3 ) 496 - 506 2007年1月

Subcellular arrangement of molecules for 2-arachidonoyl-glycerol-mediated retrograde signaling in the striatum 査読

Uchigashima Motokazu, Narushima Madoka, Fukaya Masahiro, Katona Istven, Kano Masanobu, Watanabe Masahiko

NEUROSCIENCE RESEARCH 58 S75 2007年

Depolarization-induced suppression of inhibition mediated by endocannabinoids at synapses from fast-spiking interneurons to medium spiny neurons in the striatum 査読

Madoka Narushima, Motokazu Uchigashima, Kouichi Hashimoto, Masahiko Watanabe, Masanobu Kano

EUROPEAN JOURNAL OF NEUROSCIENCE 24 ( 8 ) 2246 - 2252 2006年10月

Localization of diacylglycerol lipase-alpha around postsynaptic spine suggests close proximity between production site of an endocannabinoid, 2-arachidonoyl-glycerol, and presynaptic cannabinoid CB1 receptor. 査読

Yoshida T, Fukaya M, Uchigashima M, Miura E, Kamiya H, Kano M, Watanabe M

The Journal of neuroscience : the official journal of the Society for Neuroscience 26 4740 - 4751 2006年5月

Spine targeting of endocannabinoid synthesizing enzyme, diacylglycerol lipase-alpha in the cerebllum and hippocampus 査読

Yoshida Takayuki, Fukaya Masahiro, Uchigashima Motokazu, Miura Eriko, Kamiya Haruyuki, Kano Masanobu, Watanabe Masahiko

NEUROSCIENCE RESEARCH 55 S77 2006年

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