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SAKAGUCHI Masanori
Graduate School of Medicine / Department of Medicine
Professor

Researcher basic information

■ Research Keyword
  • 新生ニューロン
  • 記憶
  • 睡眠
  • 海馬
  • 生体脳イメージング
  • 光遺伝学
  • 深層学習
■ Research Areas
  • Life sciences / Cognitive neuroscience

Research activity information

■ Award
  • Oct. 2025 Univ Tsukuba, Teacher's award

  • Oct. 2022 筑波大学, 優秀教員表彰
    筑波大学医学医療系

  • Jan. 2021 2021 Inscopix Tech Award, SFN Global connectome

  • 2016 Society for Neuroscience, Neuroscience?2016 HotTopic, The role of adult born neurons in memory consolidation during sleep-wake cycles

  • 2015 The Adult Neurogenesis Conference, 優秀発表賞
    Sakaguchi M

  • 2014 Homeodynamics in Clocks, Sleep and Metabolism Tokyo Translational Therapeutics Meeting, 優秀発表賞, The role of adult born neurons during sleep
    Sakaguchi M

  • 2008 The Hospital for Sick Children, 優秀発表賞
    Sakaguchi M

  • 2008 The Hospital for Sick Children, Travel Award for conference, 優秀発表賞
    Sakaguchi M

  • 2007 The Hospital for Sick Children Research Institute, Restracomp Award
    Sakaguchi M

  • 2004 Keystone Symposia, Keystone Symposia Scholarship Award
    Sakaguchi M

■ Paper
  • Yuta Yamauchi, Keiko Ino, Masanori Sakaguchi, Keiichi Zempo
    Jul. 2026, ACM Transactions on Computing for Healthcare
    [Refereed]
    Scientific journal

  • Sakthivel Srinivasan, Iyo Koyanagi, Pablo Vergara, Yuteng Wang, Akinobu Ohba, Toshie Naoi, Kaspar E. Vogt, Yoan Chérasse, Noriki Kutsumura, Takeshi Sakurai, Taro Tezuka, Masanori Sakaguchi
    Abstract While memory consolidation is widely believed to require memory reactivation synchronized with theta oscillations during REM sleep, direct causal evidence linking specific neuronal ensembles to this process has been lacking. Strong theta oscillations arise in the hippocampal dentate gyrus, where a small population of principal neurons is continuously generated throughout adulthood. Although these adult-born neurons (ABNs) are known to modulate hippocampal circuits for memory, the causality between their specific information content and memory-related behavior was unknown. Here, we show that REM sleep reactivation of memory ensembles comprising as few as ~3 ABNs is necessary for fear memory consolidation. Crucially, we found that the synchronization of ABN activity with a specific theta phase is essential for associative memory consolidation. Our findings thus provide causal evidence that consolidation critically depends on both the reactivation of minimal neuronal populations and precise neuronal coordination within theta-defined temporal windows.
    Springer Science and Business Media LLC, Aug. 2025, Nature Communications, 16(1) (1)
    [Refereed]
    Scientific journal

  • Yoshifumi Arai, Mitsuaki Kashiwagi, Takeshi Kanda, Iyo Koyanagi, Masanori Sakaguchi, Masashi Yanagisawa, Yoshimasa Koyama, Yu Hayashi
    Jul. 2025, The Journal of Neuroscience
    [Refereed]
    Scientific journal

  • Haruka Sekiba, Sayuri Hirohata, Arinobu Hori, Yosuke Suga, Yuko Toshishige, Pablo Vergara, Minori Masaki, Morie Tominaga, Masashi Yanagisawa, Yoshiharu Kim, Masanori Sakaguchi
    Abstract Study objectives Sleep disturbances are reported by approximately 90% of people with post-traumatic stress disorder (PTSD), yet objective characterizations of their sleep remain inconsistent across studies. This inconsistency likely stems from the limitations of standard, single-night, laboratory-based polysomnography (PSG), which often fails to capture naturalistic sleep patterns in hypervigilant individuals. To address this critical gap, our objective was to characterize the architecture of naturalistic sleep using multi-night, in-home PSG. A more precise understanding of these sleep abnormalities is crucial for advancing our knowledge of PTSD pathophysiology and is expected to provide a foundation for developing novel, targeted therapeutic strategies. Methods In-home sleep recordings using only five electrodes and a portable PSG device were obtained from 29 people with PTSD and 29 matched healthy control individuals across multiple nights. Results Although total sleep time was similar between people with PTSD and matched healthy control individuals, people with PTSD exhibited disruptions in several rapid eye movement (REM) sleep parameters, including prolonged latency to REM sleep, shorter REM sleep episodes, fragmentation of REM sleep, and weaker REM sleep rhythmicity. Conclusion These results offer novel insights into the sleep pathophysiology of PTSD by identifying REM sleep as a core domain of disruption. These findings also underscore the urgent need for further research into how REM sleep disturbances contribute to PTSD symptoms and highlight the importance of ecologically valid sleep assessments and REM sleep-targeted therapeutic strategies for more effective treatment of PTSD. Clinical trial registration Registry: jRCT (Japan Registry of Clinical Trials): https://jrct.mhlw.go.jp/ Name: An Observational Study to Acquire Patient EEG Data for the Development of a Device Enabling Acoustic Exposure Therapy during Sleep for Post-Traumatic Stress Disorder (PTSD). Registration number: jRCT1032220029 Statement of significance Posttraumatic stress disorder (PTSD) is commonly associated with sleep-related disturbances, particularly trauma-related nightmares. Using multi-night in-home polysomnography, this study characterizes people with PTSD’ naturalistic sleep patterns. While total sleep time was comparable between people with PTSD and healthy control individuals, people with PTSD exhibited disruptions in several aspects of rapid eye movement (REM) sleep, including weaker REM sleep rhythmicity across the night. These findings offer novel insights into the sleep pathophysiology of PTSD by identifying REM sleep as a core domain of disruption and further highlight the importance of ecologically valid sleep assessments and REM sleep-targeted therapeutic strategies for more effective treatment of PTSD.
    Cold Spring Harbor Laboratory, Jul. 2025, medRxiv

  • Junzhang Chen, Iyo Koyanagi, Masanori Sakaguchi, Taro Tezuka
    The brain exhibits multiple global states that can be distinguished by wave patterns in electroencephalogram (EEG). Global brain states during the wake have been of much interest among neurologists recently, but some of the states occur in low percentages, such as less than 10% of all epochs. This scarcity makes automatic classification difficult due to class imbalance. By introducing resampling and data augmentation techniques, we developed a system based on ResNet that automatically classifies highly imbalanced brain state data. Namely, we tested oversampling, undersampling, and SMOTE on single-channel EEG recordings obtained from mice. The results showed the effectiveness of dealing with class imbalance, opening possibilities for further analysis of global brain states during the wake.
    Jul. 2025, Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference, 2025, 1 - 7, English, International magazine
    [Refereed]
    Scientific journal

  • Parimal Chavan, Takashi Kitamura, Masanori Sakaguchi
    Elsevier BV, Jul. 2025, Neurobiology of Learning and Memory, 220, 108062 - 108062
    [Refereed][Invited]
    Scientific journal

  • Pablo Vergara, Yuteng Wang, Sakthivel Srinivasan, Zhe Dong, Yu Feng, Iyo Koyanagi, Deependra Kumar, Yoan Chérasse, Toshie Naoi, Yuki Sugaya, Takeshi Sakurai, Masanobu Kano, Tristan Shuman, Denise Cai, Masashi Yanagisawa, Masanori Sakaguchi
    Abstract We developed CaliAli, a comprehensive suite designed to extract neuronal signals from one-photon calcium imaging data collected across multiple sessions in free-moving conditions in mice. CaliAli incorporates information from blood vessels and neurons to correct inter-session misalignments, making it robust against non-rigid brain deformations even after substantial changes in the field of view across sessions. This also makes CaliAli robust against high neuron overlap and changes in active neuron population across sessions. CaliAli performs computationally efficient signal extraction from concatenated video sessions that enhances the detectability of weak calcium signals. Notably, CaliAli enhanced the spatial coding accuracy of extracted hippocampal CA1 neuron activity across sessions. An optogenetic tagging experiment showed that CaliAli enhanced neuronal trackability in the dentate gyrus across a time scale of weeks. Finally, dentate gyrus neurons tracked using CaliAli exhibited stable population activity for 99 days. Overall, CaliAli advances our capacity to understand the activity dynamics of neuronal ensembles over time, which is crucial for deciphering the complex neuronal substrates of natural animal behaviors.
    Springer Science and Business Media LLC, Apr. 2025, Nature Communications, 16(1) (1), 3443
    [Refereed]
    Scientific journal

  • Yuteng Wang, Pablo Vergara, Satoshi Hasegawa, Naoki Tomita, Yoan Cherasse, Toshie Naoi, Takeshi Sakurai, Yuki Sugaya, Masanobu Kano, Masanori Sakaguchi
    Oct. 2024, bioRxiv

  • Kaizhen Li, Konstantinos Koukoutselos, Masanori Sakaguchi, Stéphane Ciocchi
    Sep. 2024, Nature Communications
    [Refereed]
    Scientific journal

  • Mitsuaki Kashiwagi, Goichi Beck, Mika Kanuka, Yoshifumi Arai, Kaeko Tanaka, Chika Tatsuzawa, Yumiko Koga, Yuki C. Saito, Marina Takagi, Yo Oishi, Masanori Sakaguchi, Kousuke Baba, Masashi Ikuno, Hodaka Yamakado, Ryosuke Takahashi, Masashi Yanagisawa, Shigeo Murayama, Takeshi Sakurai, Kazuya Sakai, Yoshimi Nakagawa, Masahiko Watanabe, Hideki Mochizuki, Yu Hayashi
    Elsevier BV, Sep. 2024, Cell, 187(22) (22), 6272 - 6289
    [Refereed]
    Scientific journal

  • Chinatsu Kawakami, Toshie Naoi, Masanori Sakaguchi
    Elsevier BV, May 2024, Biochemical and Biophysical Research Communications, 150071 - 150071, English
    [Refereed]
    Scientific journal

  • He Z., Vergara P., Sakaguchi M., Tezuka T.
    The hippocampus is an important region responsible for memory formation. Some research evidence suggests that neurons in the hippocampus discharge in a sequential order to form specific activity patterns. Multiple replayed spike sequences may represent the recurrence of an individual's memory, and scientists refer to these replayed spatiotemporal sequences as motifs. Identification and online detection of these replayed spike trains are important for studying the mechanisms of memory formation. This work aims to evaluate the detection accuracy of motifs in Calcium imaging for semisynthetic data where manually identified motifs (originating from real data) are embedded into synthetic data containing various types of noise. It allows us to accurately pinpoint the timing of motif occurrences, thereby facilitating the evaluation of our method's real-time detection performance.The action potential of a neuron is typically completed within three milliseconds, while the replay time of a complete motif usually spans several hundred milliseconds. Ideally, motifs should be detected before they end in order to investigate their functions causally through intervention. For detecting motifs, we used a non-negative matrix factorization algorithm seqNMF. We conducted tests on our method's real-time detection performance for replay events. The method exhibited the ability to perform real-time detection of replayed spike sequences within a few tens of milliseconds. It was more effective in detecting large motifs than small motifs. However, we also found that the method is susceptible to increased jitter, suggesting the importance of time-precise recording for retrieving motifs robustly.
    Apr. 2024, Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference, 2024, 1 - 7, English, International magazine
    [Refereed]
    Scientific journal

  • A noise-robust approach to estimate dimension of sleep EEG in mice using permutation entropy
    Koyama K, Sakaguchi M, Ohnishi T
    Apr. 2024, FUZZ-IEEE 2024
    [Refereed]

  • Pablo Vergara, Yuteng Wang, Sakthivel Srinivasan, Yoan Cherasse, Toshie Naoi, Yuki Sugaya, Takeshi Sakurai, Masanobu Kano, Masanori Sakaguchi
    Abstract Neuron-tracking algorithms exhibit suboptimal performance in calcium imaging when the same neurons are not consistently detected, as unmatched features hinder intersession alignment. CaliAli addresses this issue by employing an alignment-before-extraction strategy that incorporates vasculature information to improve the detectability of weak signals and maximize the number of trackable neurons. By excelling in neural remapping and high spatial overlap scenarios, CaliAli paves the way toward further understanding long-term neural network dynamics.
    Cold Spring Harbor Laboratory, May 2023, bioRxiv

  • Iyo Koyanagi, Taro Tezuka, Jiahui Yu, Sakthivel Srinivasan, Toshie Naoi, Shinnosuke Yasugaki, Ayaka Nakai, Shimpei Taniguchi, Yu Hayashi, Yasushi Nakano, Masanori Sakaguchi
    Sleep stage-specific intervention is widely used to elucidate the functions of sleep and their underlying mechanisms. For this intervention, it is imperative to accurately classify rapid-eye-movement (REM) sleep. However, the proof of fully automatic real-time REM sleep classification in vivo has not been obtained in mice. Here, we report the in vivo implementation of a system that classifies sleep stages in real-time from a single-channel electroencephalogram (EEG). It enabled REM sleep-specific intervention with 90 % sensitivity and 86 % precision without prior configuration to each mouse. We further derived systems capable of classification with higher frequency sampling and time resolution. This attach-and-go sleep staging system provides a fully automatic accurate and scalable tool for investigating the functions of sleep.
    Oct. 2022, Neuroscience research, 186, 51 - 58, English, International magazine
    [Refereed]
    Scientific journal

  • Tezuka T, Kumar D, Singh S, Koyanagi I, Naoi T, Sakaguchi M
    AbstractWe developed a real-time sleep stage classification system with a convolutional neural network using only a one-channel electro-encephalogram source from mice and universally available features in any time-series data: raw signal, spectrum, and zeitgeber time. To accommodate historical information from each subject, we included a long short-term memory recurrent neural network in combination with the universal features. The resulting system (UTSN-L) achieved 90% overall accuracy and 81% multi-class Matthews Correlation Coefficient, with particularly high-quality judgements for rapid eye movement sleep (91% sensitivity and 98% specificity). This system can enable automatic real-time interventions during rapid eye movement sleep, which has been difficult due to its relatively low abundance and short duration. Further, it eliminates the need for ordinal pre-calibration, electromyogram recording, and manual classification and thus is scalable. The code is open-source with a graphical user interface and closed feedback loop capability, making it easily adaptable to a wide variety of end-user needs. By allowing large-scale, automatic, and real-time sleep stage-specific interventions, this system can aid further investigations of the functions of sleep and the development of new therapeutic strategies for sleep-related disorders.
    Springer Science and Business Media LLC, Dec. 2021, Scientific Reports, 11(1) (1), 11151 - 11151, English, International magazine
    [Refereed]
    Scientific journal

  • Luana C Soares, Osama Al-Dalahmah, James Hillis, Christopher C Young, Isaiah Asbed, Masanori Sakaguchi, Eric O'Neill, Francis G Szele
    Galectin-3 (Gal-3) is an evolutionarily conserved and multifunctional protein that drives inflammation in disease. Gal-3's role in the central nervous system has been less studied than in the immune system. However, recent studies show it exacerbates Alzheimer's disease and is upregulated in a large variety of brain injuries, while loss of Gal-3 function can diminish symptoms of neurodegenerative diseases such as Alzheimer's. Several novel molecular pathways for Gal-3 were recently uncovered. It is a natural ligand for TREM2 (triggering receptor expressed on myeloid cells), TLR4 (Toll-like receptor 4), and IR (insulin receptor). Gal-3 regulates a number of pathways including stimulation of bone morphogenetic protein (BMP) signaling and modulating Wnt signalling in a context-dependent manner. Gal-3 typically acts in pathology but is now known to affect subventricular zone (SVZ) neurogenesis and gliogenesis in the healthy brain. Despite its myriad interactors, Gal-3 has surprisingly specific and important functions in regulating SVZ neurogenesis in disease. Gal-1, a similar lectin often co-expressed with Gal-3, also has profound effects on brain pathology and adult neurogenesis. Remarkably, Gal-3's carbohydrate recognition domain bears structural similarity to the SARS-CoV-2 virus spike protein necessary for cell entry. Gal-3 can be targeted pharmacologically and is a valid target for several diseases involving brain inflammation. The wealth of molecular pathways now known further suggest its modulation could be therapeutically useful.
    Nov. 2021, Cells, 10(11) (11), English, International magazine
    [Refereed]
    Scientific journal

  • Masaki Taniguchi, Taro Tezuka, Pablo Vergara, Sakthivel Srinivasan, Takuma Hosokawa, Yoan Cherasse, Toshie Naoi, Takeshi Sakurai, Masanori Sakaguchi
    We developed Carignan, a real-time calcium imaging software that can automatically detect activity patterns of neurons. Carignan can activate an external device when synchronized neural activity is detected in calcium imaging obtained by a one-photon (1p) miniscope. Combined with optogenetics, our software enables closed-loop experiments for investigating functions of specific types of neurons in the brain. In addition to making existing pattern detection algorithms run in real-time seamlessly, we developed a new classification module that distinguishes neurons from false-positives using deep learning. We used a combination of convolutional and recurrent neural networks to incorporate both spatial and temporal features in activity patterns. Our method performed better than existing neuron detection methods for false-positive neuron detection in terms of the F1 score. Using Carignan, experimenters can activate or suppress a group of neurons when specific neural activity is observed. Because the system uses a 1p miniscope, it can be used on the brain of a freely-moving animal, making it applicable to a wide range of experimental paradigms.
    Last, IEEE, Nov. 2021, IEEE EMBC 2021, 2021, 2997 - 3003, English, International magazine
    [Refereed]
    International conference proceedings

  • Yu J, Naoi T, Sakaguchi M
    Fear generalization is a symptom of anxiety-related disorders, including acute stress disorder and post-traumatic stress disorder. Using a contextual fear conditioning paradigm, we found that mice exposed to a similar neutral context but not a different neutral context soon after training showed fear generalization immediately after contextual fear memory consolidation (i.e., 6 h after training). This fear generalization was reflected by a change not only in the total amount but also the pattern of freezing between conditioned and generalized contexts. These results provide insight into the factors that influence fear generalization and can facilitate future studies investigating the underlying pathophysiological mechanisms of anxiety-related disorders.
    Elsevier BV, Jun. 2021, Biochemical and Biophysical Research Communications, 558, 102 - 106, English, International magazine
    [Refereed]
    Scientific journal

  • Vergara P, Kumar D, Srinivasan S, Koyanagi I, Naoi T, Singh S, Sakaguchi M
    The mammalian hippocampal dentate gyrus is a unique memory circuit in which a subset of neurons is continuously generated throughout the lifespan. Previous studies have shown that the dentate gyrus neuronal population can hold fear memory traces (i.e., engrams) and that adult-born neurons (ABNs) support this process. However, it is unclear whether ABNs themselves hold fear memory traces. Therefore, we analyzed ABN activity at a population level across a fear conditioning paradigm. We found that fear learning did not recruit a distinct ABN population. In sharp contrast, a completely different ABN population was recruited during fear memory retrieval. We further provide evidence that ABN population activity remaps over time during the consolidation period. These results suggest that ABNs support the establishment of a fear memory trace in a different manner to directly holding the memory. Moreover, this activity remapping process in ABNs may support the segregation of memories formed at different times. These results provide new insight into the role of adult neurogenesis in the mammalian memory system.
    Mar. 2021, International journal of molecular sciences, 22(6) (6), English, International magazine
    [Refereed]
    Scientific journal

  • Koyanagi I, Sonomura K, Naoi T, Ohnishi T, Kaneko N, Sawamoto K, Sato T, Sakaguchi M
    Metabolites underlying brain function and pathology are not as well understood as genes. Here, we applied a novel metabolomics approach to further understand the mechanisms of memory processing in sleep. As hippocampal dentate gyrus neurons are known to consolidate contextual fear memory, we analyzed real-time changes in metabolites in the dentate gyrus in different sleep-wake states in mice. Throughout the study, we consistently detected more than > 200 metabolites. Metabolite profiles changed dramactically upon sleep-wake state transitions, leading to a clear separation of phenotypes between wakefulness and sleep. By contrast, contextual fear memory consolidation induced less obvious metabolite phenotypes. However, changes in purine metabolites were observed upon both sleep-wake state transitions and contextual fear memory consolidation. Dietary supplementation of certain purine metabolites impaired correlations between conditioned fear responses before and after memory consolidation. These results point toward the importance of purine metabolism in fear memory processing during sleep.
    Feb. 2021, Molecular brain, 14(1) (1), 30 - 30, English, International magazine
    [Refereed]
    Scientific journal

  • Ohba A, Sakaguchi M
    Medknow, 2021, Neural Regeneration Research, 17(2) (2), 307 - 307, English, International magazine
    [Refereed]
    Scientific journal

  • Calcium imaging of adult-born neurons in freely moving mice
    Carrier-Ruiz A, Sugaya Y, Kumar D, Vergara P, Koyanagi I, Srinivasan S, Naoi T, Kano M, Sakaguchi M
    2021, STAR Protocols
    [Refereed]
    Scientific journal

  • Vergara P, Sakaguchi M
    The mammalian hippocampus generates new neurons that incorporate into existing neuronal networks throughout the lifespan, which bestows a unique form of cellular plasticity to the memory system. Recently, we found that hippocampal adult-born neurons (ABNs) that were active during learning reactivate during subsequent rapid eye movement (REM) sleep and provided causal evidence that ABN activity during REM sleep is necessary for memory consolidation. Here, we describe the potential underlying mechanisms by highlighting distinct characteristics of ABNs including decoupled firing from local oscillations and ability to undergo profound synaptic remodeling in response to experience. We further discuss whether ABNs constitute the conventional definition of engram cells by focusing on their active and passive roles in the memory system. This synthesis of evidence helps advance our thinking on the unique mechanisms by which ABNs contribute to memory consolidation.
    Frontiers Media SA, Nov. 2020, Frontiers in Cellular Neuroscience, 14, English
    [Refereed]
    Scientific journal

  • Kumar D, Koyanagi I, Carrier-Ruiz A, Vergara P, Srinivasan S, Sugaya Y, Kasuya M, Yu T, Vogt KE, Muratani M, Ohnishi T, Singh S, Teixeira CM, Chérasse Y, Naoi T, Wang S, Nondhalee P, Osman BAH, Kaneko N, Sawamoto K, Kernie SG, Sakurai T, McHugh TJ, Kano M, Yanagisawa M, Sakaguchi M
    The occurrence of dreaming during rapid eye movement (REM) sleep prompts interest in the role of REM sleep in hippocampal-dependent episodic memory. Within the mammalian hippocampus, the dentate gyrus (DG) has the unique characteristic of exhibiting neurogenesis persisting into adulthood. Despite their small numbers and sparse activity, adult-born neurons (ABNs) in the DG play critical roles in memory; however, their memory function during sleep is unknown. Here, we investigate whether young ABN activity contributes to memory consolidation during sleep using Ca2+ imaging in freely moving mice. We found that contextual fear learning recruits a population of young ABNs that are reactivated during subsequent REM sleep against a backdrop of overall reduced ABN activity. Optogenetic silencing of this sparse ABN activity during REM sleep alters the structural remodeling of spines on ABN dendrites and impairs memory consolidation. These findings provide a causal link between ABN activity during REM sleep and memory consolidation.
    Elsevier BV, Aug. 2020, Neuron, 107(3) (3), 552 - 565.e10, English, International magazine
    [Refereed]
    Scientific journal

  • Maezono E.B.S, Kanuka M, Tatsuzawa C, Morita M, Kawano T, Kashiwagi M, Nondhalee P, Sakaguchi M, Saito T, Saido T, Hayashi Y
    Society for Neuroscience, Mar. 2020, Eneuro, 7(2) (2), 0093 - 20.2020, English
    [Refereed]
    Scientific journal

  • Srinivasan S, Hosokawa T, Vergara P, Chérasse Y, Naoi T, Sakurai T, Sakaguchi M
    Elsevier {BV}, Sep. 2019, Biochemical and Biophysical Research Communications, 517(3) (3), 520 - 524, English
    [Refereed]
    Scientific journal

  • Koyanagi I, Akers KG, Vergara-García P, Srinivasan S, Sakurai T, Sakaguchi M
    2019, Neural Regeneration Research, 14(1) (1), 20 - 23, English
    [Refereed]
    Scientific journal

  • Akers KG, Chérasse Y, Fujita Y, Sakthivel S, Sakurai T, Sakaguchi M
    Wiley, 2018, Stem Cells, 36(7) (7), 969 - 976, English
    [Refereed]
    Scientific journal

  • Purple R, Sakurai T, Sakaguchi M
    2017, Scientific Reports, 7, 46247, English
    [Refereed]
    Scientific journal

  • Fujinaka A, Li R, Hayashi M, Kumar D, Changarathil G, Naito K, Miki K, Nishiyama T, Lazarus M, Sakurai T, Kee N, Nakajima S, Wang SH, Sakaguchi M
    2016, Molecular Brain, 9(1) (1), 2, English
    [Refereed]
    Scientific journal

  • Sakaguchi M, Kim K, Yu LMY, Hashikawa Y, Sekine Y, Okumura Y, Kawano M, Hayashi M, Kumar D, Boyden ES, McHugh TJ, Hayashi Y
    2015, PLoS ONE, 10(6) (6), e0130163
    [Refereed]
    Scientific journal

  • Arruda-Carvalho M, Akers KG, Guskjolen AJ, Sakaguchi M, Josselyn S, Frankland PW
    2014, Journal of Neuroscience, 34(47) (47), 15793 - 15803, English
    [Refereed]
    Scientific journal

  • Sakaguchi M, Okano H
    Lead, 2012, Developmental Neurobiology, 72(7) (7), 1059 - 1067, English
    [Refereed]
    Scientific journal

  • Hirota Y, Sawada M, Kida Y, Huang SH, Yamada O, Sakaguchi M, Ogura T, Okano H, Sawamoto K
    2012, Stem Cells, 30(8) (8), 1726 - 1733, English
    [Refereed]
    Scientific journal

  • Sakaguchi M, Hayashi Y
    2012, Molecular Brain, 5(1) (1), 32, English
    [Refereed]
    Scientific journal

  • Imaizumi Y, Sakaguchi M, Morishita T, Ito M, Poirier F, Sawamoto K, Okano H
    2011, Molecular Brain, 4(1) (1), 7 - 7, English, International magazine
    [Refereed]
    Scientific journal

  • Leslie AT, Akers KG, Krakowski A, Stone S, Sakaguchi M, Arruda-Calvalho M, Frankland PW
    2011, Translational Psychiatry, 1(e35) (e35), English
    [Refereed]
    Scientific journal

  • Yamane J, Ishibashi S, Sakaguchi M, Kuroiwa T, Kanemura Y, Nakamura M, Miyoshi H, Sawamoto K, Toyama Y, Mizusawa H, Okano H
    2011, Molecular Brain, 4(1) (1), 35, English
    [Refereed]
    Scientific journal

  • Sakaguchi M, Arruda-Carvalho M, Kang NH, Imaizumi Y, Poirier F, Okano H, Frankland PW
    Lead, 2011, Molecular Brain, 4(1) (1), 33, English
    [Refereed]
    Scientific journal

  • Arruda-Carvalho M*, Sakaguchi M*, Akers KG, Josselyn SA, Frankland PW, *equally contributed
    Lead, 2011, Journal of Neuroscience, 31(42) (42), 15113 - 15127, English
    [Refereed]
    Scientific journal

  • Stone S, Teixeira CM, Zaslavsky K, Wheeler AL, Canabal AM, Wang AH, Sakaguchi M, Lozano AM, Frankland PW
    2011, Hippocampus, 21(12) (12), 1348 - 1362, English
    [Refereed]
    Scientific journal

  • Hirota Y, Meunier A, Huang S, Shimozawa T, Yamada O, Kida YS, Inoue M, Ito T, Kato H, Sakaguchi M, Sunabori T, Nakaya M, Nonaka S, Ogura T, Higuchi H, Okano H, Spassky N, Sawamoto K
    Sep. 2010, Development, 137(18) (18), 3037 - 3046, English
    [Refereed]
    Scientific journal

  • Sakaguchi M, Imaizumi Y, Shingo T, Tada H, Hayama K, Yamada O, Morishita T, Kadoya T, Uchiyama N, Shimazaki T, Kuno A, Poirier F, Hirabayashi J, Sawamoto K, Okano H
    Lead, Jun. 2010, Journal of Neurochemistry, 113(6) (6), 1516 - 1524, English
    [Refereed]
    Scientific journal

  • Yamane J, Nakamura M, Iwanami A, Sakaguchi M, Katoh H, Yamada M, Momoshima M, Miyao S, Ishii K, Tamaoki N, Nomura T, Okano HJ, Kanemura Y, Toyama Y, Okano H
    May 2010, Journal of Neuroscience Research, 88(7) (7), 1394 - 1405, English
    [Refereed]
    Scientific journal

  • Akers KG, Sakaguchi M, Arruda-Carvalho M
    2010, Journal of Neuroscience, 30(13) (13), 4523 - 4525
    [Refereed]
    Scientific journal

  • Ikeda M, Hirota Y, Sakaguchi M, Yamada O, Kida YS, Ogura T, Otsuka T, Okano H, Sawamoto K
    2010, Stem Cells, 28(11) (11), 2017 - 2026
    [Refereed]
    Scientific journal

  • Frankland PW, Sakaguchi M, Arruda-Carvalho M
    2008, Molecular Brain, 1, 5, English
    [Refereed]

  • Adachi K, Mirzadesh Z, Sakaguchi M, Yamashita T, Nikolcheva T, Gotoh Y, Peltz G, Gong L, Kawase T, Alvarez-Buylla A, Okano H, Sawamoto K
    Nov. 2007, Stem Cells, 25(11) (11), 2827 - 2836, English
    [Refereed]
    Scientific journal

  • Ishibashi S, Kuroiwa T, Sakaguchi M, Sun L, Kadoya T, Okano H, Mizusawa H
    Oct. 2007, Experimental Neurology, 207(2) (2), 302 - 313, English
    [Refereed]
    Scientific journal

  • Okano H, Sakaguchi M, Ohki K, Suzuki N, Sawamoto K
    Sep. 2007, Journal of Neurochemistry, 102(5) (5), 1459 - 1465, English
    [Refereed]

  • Sakaguchi M, Imaizumi Y, Okano H
    Lead, May 2007, Cellular and Molecular Life Sciences, 64(10) (10), 1254 - 1258, English
    [Refereed]

  • Yamashita T, Ninomiya M, Acosta PH, García-Verdugo JM, Sunabori T, Sakaguchi M, Adachi K, Kojima T, Hirota Y, Kawase T, Araki N, Abe K, Okano H, Sawamoto K
    Recent studies have revealed that the adult mammalian brain has the capacity to regenerate some neurons after various insults. However, the precise mechanism of insult-induced neurogenesis has not been demonstrated. In the normal brain, GFAP-expressing cells in the subventricular zone (SVZ) of the lateral ventricles include a neurogenic cell population that gives rise to olfactory bulb neurons only. Herein, we report evidence that, after a stroke, these cells are capable of producing new neurons outside the olfactory bulbs. SVZ GFAP-expressing cells labeled by a cell-type-specific viral infection method were found to generate neuroblasts that migrated toward the injured striatum after middle cerebral artery occlusion. These neuroblasts in the striatum formed elongated chain-like cell aggregates similar to those in the normal SVZ, and these chains were observed to be closely associated with thin astrocytic processes and blood vessels. Finally, long-term tracing of the green fluorescent-labeled cells with a Cre-loxP system revealed that the SVZ-derived neuroblasts differentiated into mature neurons in the striatum, in which they expressed neuronal-specific nuclear protein and formed synapses with neighboring striatal cells. These results highlight the role of the SVZ in neuronal regeneration after a stroke and its potential as an important therapeutic target for various neurological disorders.
    Jun. 2006, The Journal of neuroscience : the official journal of the Society for Neuroscience, 26(24) (24), 6627 - 36, English, International magazine
    [Refereed]
    Scientific journal

  • Sakaguchi M, Shingo T, Shimazaki T, Okano HJ, Shiwa M, Ishibashi S, Oguro H, Ninomiya M, Kadoya T, Horie H, Shibuya A, Mizusawa H, Poirier F, Nakauchi H, Sawamoto K, Okano H
    Lead, May 2006, Proceedings of The National Academy of Sciences of The United States of America, 103(18) (18), 7112 - 7117, English
    [Refereed]
    Scientific journal

  • Neural stem cells: Isolation and self-renewal
    Hideyuki Okano, Jun Kohyama, Hiroyuki Ohba, Masanori Sakaguchi, Akinori Tokunaga, Takuya Shimazaki, Hirotaka James Okano
    CRC Press, Jan. 2006, Tissue Stem Cells, 55 - 70, English
    In book

  • A method for gene transfer, single isolation and in vitro assay for neural stem cells
    Sakaguchi M, Sawamoto K, Shimazaki T, Kitamura T, Shibuya A, Okano H
    Lead, Jan. 2005, Inflammation and Regeneration, 25(1) (1), 50 - 54, English
    [Refereed]
    Scientific journal

  • Ishibashi S, Sakaguchi M, Kuroiwa T, Yamasaki M, Kanemura Y, Ichinose S, Onodera M, Shimazaki T, Okano H, Mizusawa H
    Oct. 2004, Journal of Neuroscience Research, 78(2) (2), 215 - 223, English
    [Refereed]
    Scientific journal

  • Mikami Y, Okano H, Sakaguchi M, Nakamura M, Shimazaki T, Okano HJ, Kawakami Y, Toyama Y, Toda M
    May 2004, Journal of Neuroscience Research, 76(4) (4), 453 - 465, English
    [Refereed]
    Scientific journal

  • Ohba H, Chiyoda T, Endo E, Yano M, Hayakawa Y, Sakaguchi M
    Apr. 2004, Neuroscience Letters, 358(3) (3), 157 - 160, English
    [Refereed]
    Scientific journal

■ MISC
  • 菅谷 佑樹, 坂口 昌徳
    (株)医学書院, Jul. 2021, BRAIN and NERVE: 神経研究の進歩, 73(7) (7), 0813 - 0817, Japanese

  • 局所脳虚血モデルに対するガレクチン-1遺伝子導入ヒト神経幹細胞移植効果の検討
    石橋 哲, 坂口 昌徳, 山根 淳一, 金村 米博, 中村 雅也, 澤本 和延, 戸山 芳昭, 岡野 栄之, 水澤 英洋
    (一社)日本神経学会, Dec. 2012, 臨床神経学, 52(12) (12), 1404 - 1404, Japanese

  • 非筋細胞ミオシンIIによるマウス上衣細胞繊毛の平面極性制御
    廣田ゆき, MEUNIER Alice, 黄詩惠, 下澤東吾, 山田理, 木田泰之, 井上雅史, 伊東翼, 加藤寛子, 坂口昌徳, 砂堀毅彦, 中谷雅明, 野中茂紀, 小椋利彦, 樋口秀男, 岡野栄之, SPASSKY Nathalie, 澤本和延
    01 Mar. 2011, Nagoya Med J, 51(4) (4), 219, Japanese

  • Yoichi Imaizumi, Masanori Sakaguchi, Tsuyoshi Morishita, Mamoru Ito, Francoise Poirier, Kazunobu Sawamoto, Hideyuki Okano
    2010, NEUROSCIENCE RESEARCH, 68, E365 - E365, English
    Summary international conference

  • Makiko Ikeda, Yuki Hirota, Masanori Sakaguchi, Osamu Yamada, Yasuyuki Kida, Tashihiko Ogura, Takanobu Otsuka, Hideyuki Okano, Kazunobu Sawamoto
    2009, NEUROSCIENCE RESEARCH, 65, S54 - S54, English
    Summary international conference

  • ROLE OF WNT/BETA-CATENIN SIGNALING IN NEUROGENESIS IN THE ADULT MOUSE SUBVENTRICULAR ZONE
    Kazunobu Sawamoto, Kazuhide Adachi, Makiko Ikeda, Yuki Hirota, Masanori Sakaguchi, Osamu Yamada, Yasuyuki Kida, Toshihiko Ogura, Zaman Mirzadeh, Tania Nikolcheva, Yukiko Gotoh, Gary Peltz, Leyi Gong, Arturo Alvarez-Buylla, Takanobu Ohtsuka, Hideyuki Okano
    2009, JOURNAL OF PHYSIOLOGICAL SCIENCES, 59, 442 - 442, English
    Summary international conference

  • Expression and function of Galectin-1 in adult neurogenesis of the hippocampus
    Yoichi Imaizumi, Masanori Sakaguchi, Francoise Poirier, Mamoru Ito, Tsuyoshi Morishita, Kazunobu Sawamoto, Hideyuki Okano
    2008, NEUROSCIENCE RESEARCH, 61, S239 - S239, English
    Summary international conference

  • Galectin
    Y Imaizumi, M Sakaguchi, H Okano
    Oct. 2007, 分子細胞治療, 6, 80 - 81, Japanese
    Introduction scientific journal

  • 糖鎖結合蛋白質Galectin1は成体脳内の神経幹細胞の増殖を促進させる
    坂口昌徳, 今泉陽一, 澤本和延, 岡野栄之
    Aug. 2006, 細胞工学, 25(8) (8), 912 - 913
    [Invited]

  • Role of beta-catenin signaling in regulating proliferation of transit-amplifying cells in the adult mouse subventricular zone
    Kazuhide Adachi, Masanori Sakaguchi, Toru Yamashita, Yuko Fujita, Yukiko Gotoh, Arturo Alvarez-Buylla, Takeshi Kawase, Hideyuki Okano, Kazunobu Sawamoto
    2006, NEUROSCIENCE RESEARCH, 55, S53 - S53, English
    Summary international conference

  • Transplantation of human embryonic neural stem cells transfected by lentiviral vector to express h-Galectin1 after spinal cord injury in primates
    J Yamane, A Iwanami, H Katoh, K Ishii, M Yamada, S Momoshima, S Miyao, Y Tanioka, N Tamaoki, T Nomura, M Sakaguchi, J Okano, M Nakamura, Y Toyama, H Okano
    Oct. 2005, JOURNAL OF NEUROTRAUMA, 22(10) (10), 1172 - 1172, English
    Summary international conference

  • 神経幹細胞 (第1土曜特集 脳科学の先端的研究--遺伝子から高次機能まで) -- (神経の発生)
    二宮充喜子, 澤本和延, 坂口昌徳
    医歯薬出版, 05 Mar. 2005, 医学のあゆみ, 212(10) (10), 865 - 868, Japanese

  • 局所脳虚血モデルに対するヒト神経幹細胞移植 シナプス形成能の検討
    石橋 哲, 黒岩 俊彦, 市ノ瀬 志津子, 坂口 昌徳, 島崎 琢也, 金村 米博, 山崎 麻美, 小野寺 雅史, 岡野 栄之, 水澤 英洋
    (一社)日本神経学会, Dec. 2004, 臨床神経学, 44(12) (12), 1022 - 1022, Japanese

  • スナネズミ局所脳虚血モデルに対するヒト神経幹細胞移植療法の検討
    石橋 哲, 水澤 英洋, 黒岩 俊彦, 坂口 昌徳, 島崎 琢也, 岡野 栄之, 金村 米博, 山崎 麻美
    (一社)日本神経学会, Dec. 2003, 臨床神経学, 43(12) (12), 943 - 943, Japanese

■ Books And Other Publications
  • 睡眠学第2版
    小柳伊代, 坂口昌徳
    睡眠と記憶, 朝倉書店, Dec. 2019

  • トラウマ記憶を弱めるには ? マウスの記憶・睡眠研究から考えるPTSDケア
    小柳伊代, 李若詩, 藤中彩乃, 坂口昌徳
    AdademistJournal, 2017, https://academist-cf.com/journal/?p=5352

  • トラウマ直後の環境条件の記憶汎化における重要性-心的外傷後ストレス障害(PTSD)治療における意義
    Oishi Makoto, Nakajima Satomi, Sakaguchi Masanori
    医歯薬出版(株), 2016, p1209-1210

  • 脳内で新生するニューロンと、中枢神経再生への応用
    Sakaguchi M
    クバプロ, 2016, p263-279, ISBN: 9784878051456

  • Recombinant sugar binding proteins and their functional analysis: Galectin-1
    坂口昌徳, 澤本和延, 岡野栄之
    JCGGDB, 2014, https://jcggdb.jp/GlycoPOD/protocolShow.action?nodeId=x104

  • Galectin.
    Imaizumi Y, Sakaguchi M, Hideyuki O
    先端医学社, 2007, p80-81

  • The carbohydrate binding protein, Galectin-1 promotes proliferation of adult neural stem cells.
    Sakaguchi M, Imaizumi Y, Sawamoto K, Okano H
    羊土社, 2006, pp912-913

  • Neural stem cells: Isolation and self-renewal.
    Okano H, Kohyama J, Ohba H, Sakaguchi M, Tokunaga A, Shimazaki T, Okano HJ
    Taylor & Francis Group, 2006, pp55-70

  • Neural Stem Cells
    Ninomiya M, Sawamoto K, Sakaguchi M, Okano H
    医歯薬出版(株), 2005, pp865-868

  • Development and regeneration of nervous system.
    Sakaguchi M, Sunabori K, Sawamoto K, Okano H
    羊土社, 2005, pp139-148

  • Neuro-regenerative therapy - future therapeutic strategy
    Sakaguchi M, Sawamoto K, Okano H
    中山書店, 2005, pp88-92

■ Lectures, oral presentations, etc.
  • Hippocampal Adult-Born Neurons for Memory Consolidation during REM Sleep
    坂口昌徳
    U of T Brain and Bee seminar, Nov. 2022
    [Invited]
    Invited oral presentation

  • CaliAli (Calcium imaging inter-session alignment): neuronal tracing utilizing vasculature in calcium imaging
    Pablo Vergara, Sakthivel Srinivasan, Yuteng Wang, Toshie Naoi, Yuki Sugaya, Masanobu Kano, Masanori Sakaguchi
    Frankland lab seminar, Nov. 2022

  • Fully automatic sleep stage-specific intervention using single EEG in mice
    Iyo Koyanagi, Taro Tezuka, Jiahui Yu, Sakthivel Srinivasan, Toshie Naoi, Shinnosuke Yasugaki, Ayaka Nakai, Shimpei Taniguchi, Yu Hayashi, Yasushi Nakano, Masanori Sakaguchi
    Frankland lab seminar, Nov. 2022

  • Transient recruitment of adult-born neurons for fear memory consolidation in REM sleep
    Sakthivel Srinivasan, Iyo Koyanagi, Pablo Vergara, Yuteng Wang, Jiahui Yu, Toshie Naoi, Kaspar E. Vog, Yoan Chérasse, Takeshi Sakurai, Noriki Kutsumrura, Taro Tezuka, Masanori Sakaguchi
    北米神経学会, Nov. 2022
    Poster presentation

  • CaliAli (Calcium imaging inter-session alignment): neuronal tracing utilizing vasculature in calcium imaging
    Pablo Vergara, Sakthivel Srinivasan, Yuteng Wang, Toshie Naoi, Yuki Sugaya, Masanobu Kano, Masanori Sakaguchi
    北米神経学会, Nov. 2022

  • Fully automatic sleep stage-specific intervention using single EEG in mice
    Iyo Koyanagi, Taro Tezuka, Jiahui Yu, Sakthivel Srinivasan, Toshie Naoi, Shinnosuke Yasugaki, Ayaka Nakai, Shimpei Taniguchi, Yu Hayashi, Yasushi Nakano, Masanori Sakaguchi
    北米神経学会, Nov. 2022

  • Transient recruitment of adult-born neurons for fear memory consolidation in REM sleep
    Sakthivel Srinivasan, Iyo Koyanagi, Pablo Vergara, Yuteng Wang, Jiahui Yu, Toshie Naoi, Kaspar E. Vog, Yoan Chérasse, Takeshi Sakurai, Noriki Kutsumrura, Taro Tezuka, Masanori Sakaguchi
    MCCS 2022, Nov. 2022
    Poster presentation

  • Fully automatic sleep stage-specific intervention using single EEG in mice
    Iyo Koyanagi, Taro Tezuka, Jiahui Yu, Sakthivel Srinivasan, Toshie Naoi, Shinnosuke Yasugaki, Ayaka Nakai, Shimpei Taniguchi, Yu Hayashi, Yasushi Nakano, Masanori Sakaguchi
    MCCS 2022, Nov. 2022
    Poster presentation

  • CaliAli (Calcium imaging inter-session alignment): neuronal tracing utilizing vasculature in calcium imaging
    Pablo Vergara, Sakthivel Srinivasan, Yuteng Wang, Toshie Naoi, Yuki Sugaya, Masanobu Kano, Masanori Sakaguchi
    MCCS 2022, Nov. 2022
    Poster presentation

  • Memory consolidation during sleep by the adult-born neurons
    坂口昌徳
    第19回成体脳ニューロン新生懇談会

  • Adult-born neuron activity in the establishment of fear generalization
    Jiahui Yu, Pablo Vergara, Toshie Naoi, Yuteng Wang, Yoan Chérasse, Takeshi Sakurai, Masanori Sakaguchi
    日本神経科学会, Jul. 2022
    Poster presentation

  • 睡眠中の恐怖記憶処理メカニズムの解明とPTSDの治療開発
    坂口昌徳
    第118回日本精神神経学会学術総会, Jun. 2022
    [Invited]
    Invited oral presentation

  • Transient recruitment of adult-born neurons for fear memory consolidation in REM sleep
    Sakthivel Srinivasan, Iyo Koyanagi, Pablo Vergara, Yuteng Wang, Jiahui Yu, Toshie Naoi, Kaspar E. Vog, Yoan Chérasse, Takeshi Sakurai, Noriki Kutsumrura, Taro Tezuka, Masanori Sakaguchi
    CREST Opt Bio - the 10th Annual IIIS Symposium, Mar. 2022
    Poster presentation

  • Mechanisms of adult-born neurons for memory consolidation during sleep
    Iyo Koyanagi, Yuteng Wang, Sakthivel Srinivasan, Jiahui Yu, Toshie Naoi, Akinobu Ohba, Deependra Kumar, Pei-Hsi Wu, Kaspar Vog, Shinji Matsuda, Yoan Cherasse, Takeshi Sakurai, Masashi Yanagisawa, Michisuke Yuzaki, Masanori Sakaguchi
    CREST Opt Bio - the 10th Annual IIIS Symposium, Mar. 2022
    Poster presentation

  • A tool for inter-session alignment of 1-photon calcium imaging data allowing tracking neurons in a non-rigidly moving brain.
    Pablo Vergara, Sakthivel Srinivasan, Toshie Naoi, Yoan Cherasse, Takeshi Sakurai, Masanori Sakaguchi
    CREST Opt Bio - the 10th Annual IIIS Symposium, Mar. 2022
    Poster presentation

  • Synchronous young and matured neuron activity for memory consolidation
    Yuteng Wang, Pablo Vergara, Sakthivel Srinivasan, Jiahui Yu, Toshie Naoi, Yoan Cherasse, TakeshiSakurai, Masanori Sakaguchi
    CREST Opt Bio - the 10th Annual IIIS Symposium, Mar. 2022
    Poster presentation

  • Adult-born neuron activity in the establishment of fear generalization
    Jiahui Yu, Pablo Vergara, Toshie Naoi, Yuteng Wang, Yoan Cherasse, Takeshi Sakurai, Masanori Sakaguchi
    CREST Opt Bio - the 10th Annual IIIS Symposium, Mar. 2022
    Poster presentation

  • 睡眠中の恐怖記憶処理機構
    坂口昌徳
    子どもの発達とトラウマ研究会, Mar. 2022
    [Invited]
    Invited oral presentation

  • 睡眠中の記憶固定化における脳神経再生の役割
    坂口昌徳
    日本睡眠学会第 46 回定期学術 集会, Sep. 2021
    [Invited]
    Invited oral presentation

  • Mechanisms of fear memory consolidation during REM sleep
    坂口昌徳
    生理研研究会2021 記憶研究会2021, Sep. 2021
    [Invited]
    Invited oral presentation

  • 睡眠中のトラウマ記憶処理メカニズム
    坂口昌徳
    第13回日本不安症学会学術大会, May 2021
    [Invited]
    Invited oral presentation

  • Necessity of adult-born neurons for memory consolidation during REM sleep
    Masanori Sakaguchi
    Toyama Forum for Academic Summit on "Dynamic Brain", Dec. 2019, English, Toyama, Japan
    [Invited]

  • The mechanism of fear memory consolidation during sleep using animal model
    Masanori Sakaguchi
    The 49th Japanese Society of Neurophsychopharmacology, Oct. 2019, English, Fukuoka, Japan
    [Invited]

  • Function of adult-born neurons in maturation of fear memory engram during sleep
    Masanori Sakaguchi
    The 10th IBRO World congress of Neuroscience, Sep. 2019, English, Daegu, Korea
    [Invited]

  • The fear memory processing during sleep for a new therapy of PTSD
    Masanori Sakaguchi
    The 18th Japanese Traumatic Stress Conference, Jun. 2019, English, Kyoto, Japan
    [Invited]

  • Associative memory formed by the hippocampal adult-born neurons during sleep
    Masanori Sakaguchi
    Annual adult-neurogenesis conference, Feb. 2019, English, Osaka, Japan
    [Invited]

  • Sleep and memory consolidation
    Deependra Kumar, Iyo Koyanagi, Alvaro Carrier Ruiz, Pablo Vergara, Yuki Sugaya, Sakthivel Srinivasan, Masatoshi Kasuya, Tony Yu, Kaspar Vogt, Masafumi Muratani, Takaaki Ohnishi, Sima Singh, Catia M Teixeir, Nondhalee Pimpimon, Toshie Naoi, Thomas G McHugh, Steven G Kernie, Masanobu Kano, Takeshi Sakurai, Masashi Yanagisawa, Masanori Sakaguchi
    日本睡眠学会, 2018, English, Sapporo convention center, Sapporo, Hokkaido, Japan
    [Invited]

  • 成体脳で再生を続けるニューロンが、睡眠中に恐怖記憶の固定化に果たす役割
    坂口昌徳
    医療心理懇話会第3回集会, 2018, Japanese, Shinjyuku, Tokyo
    [Invited]

  • Memory consolidation during sleep and its mechanism for clinical insights
    Sakaguchi M, Srinivasan S, Koyanagi I, Nondhalee P, Yu T, Vogt K, Singh S, Obo H, Naoi T, Kernie T G, Sakurai T, Yanagisawa M, Kumar D
    Asian Society of Sleep Medicine 2018 Cogress, 2018, English, TBA, Seoul, Korea
    [Invited]

  • Mechanism of memory consolidation during sleep
    Sakaguchi M, Koyanagi I, Srinivasan S, Nondhalee P, Singh S, Yu T, Vogt K, Obo H, Naoi T, Kernie S G, Sakurai T, Yanagisawa M, Kumar D
    NIPS conference: An approach to the integrative understanding of learning and memory, 2017, English, National Institute for Physiological Sciences, Okazaki, Aichi, Japan
    [Invited]

  • 脳と心のフロンティア〜「知」と「療」の連携
    Sakaguchi M, Koyanagi I, Srinivasan S, Nondhalee P, Singh S, Yu T, Vogt K, Obo H, Naoi T, Kernie S G, Sakurai T, YanagisawaM, Kumar D
    The 39th Japanese Society for Biological Psychology, The 47th Japanese Society for Neuropsychopharmacology, 2017, Japanese, Sapporo convention center, Sapporo, Hokkaido, Japan
    [Invited]

  • The role of adult-born neurons in memory consolidation during sleep
    KumarD, Koyanagi I, Srinivasan S, Nondhalee P, Singh S, Yu T, Vogt K, Obo H, Naoi T, Kernie S G, Sakurai T, Yanagisawa M, Sakaguchi M
    Indian society for sleep research,, 2017, English, The International Centre Goa, Goa, India
    [Invited]

  • Function of the adult-born neurons for memory consolidation during sleep
    Sakaguchi M, Srinivasan S, Koyanagi I, Nondhalee P, Yu T, Vogt K, Singh S, Obo H, Naoi T, Kernie T G, Sakurai T, Yanagisawa M, Kumar D
    The 20th KSBNS annual meeting, 2017, English, Grand Hilton Hotel, Seoul, Korea
    [Invited]

  • EEG brain rhythms for memory consolidation during sleep
    Nondhalee P, Ohnishi T, Kumar D, Singh S, Koyanagi I, Obo H, Sakurai T, Sakaguchi M
    The 40th Annual Meeting of the Japan Neuroscience Society, 2017, English, Makuhari Messe, Chiba, Japan,
    [Invited]

  • Active Role of Sleep in Forgetting of Memory
    Li R, Koyanagi I, Sakurai T, Sakaguchi M
    The 40th Annual Meeting of the Japan Neuroscience Society, 2017, English, Makuhari Messe, Chiba, Japan,
    [Invited]

  • Molecular mechanisms of memory consolidation during sleep
    Koyanagi I, Sonomura K, Kumar D, Obo H, Sato T, Sakurai T, Sakaguchi M
    The 40th Annual Meeting of the Japan Neuroscience Society, 2017, English, Makuhari Messe, Chiba, Japan
    [Invited]

  • Function of the adult-born neurons in memory consolidation during sleep
    Sakaguchi M
    Peking Univ. seminar, 2017, English, Peking University, Beijing, China
    [Invited]

  • Function of adult-born neurons in memory consolidation during sleep
    Sakaguchi M
    Neurogenesis in Developing and Adult Primate Brain - Challenges for Therapeutic Applications, 2017, English, Cherno More Hotel, Verna, Bulgaria
    [Invited]

  • Metabolomic analysis for memory consolidation of the adult-born neurons during sleep
    Sakaguchi M
    The Adult Neurogenesis Conference, 2017, English, Shiga Medical Univ, Shiga, Japan,
    [Invited]

  • マウス光遺伝学を用いたトラウマ記憶の脳内処理過程,
    Sakaguchi M
    医療心理懇話会演題, 2016, Japanese, フクラシア東京, 東京
    [Invited]

  • Function of the adult-born neurons in memory consolidation during sleep
    Deependra K, Sakaguchi M
    記憶研究会, 2016, English, 東京大学, 東京
    [Invited]

  • The activity of adult born neurons are necessary for memory consolidation during sleep
    Sakaguchi M
    NCTC seminar, 2016, English, National Chiao-Tung University, Hsinchu(Taiwan)
    [Invited]

  • 新生神経の光制御にて明らかにする,記憶と睡眠の関係
    Sakaguchi M
    第89回日本薬理学会年会, 2016, Japanese, パシフィコ横浜,神奈川
    [Invited]

  • 成体脳で新生するニューロンが、睡眠中の記憶の固定化に果 たす役割り
    Sakaguchi M
    日本睡眠学会第 41 回定期学術集会, 2016, Japanese, 京王プラザホテル,東京
    [Invited]

  • Adult neurogenesis plays critical role in sleep stage dependent memory formation
    Sakaguchi M
    脳肝センターシンポジウム, 2016, English, 全日空ホテル,石川
    [Invited]

  • 新生ニューロンの光制御にて明らかにする,記憶と睡眠の関係」,シンポジウム演者,第8 9回日本薬理学会年会
    Sakaguchi M
    第8 9回日本薬理学会年会, 2016, Japanese, 横浜
    [Invited]

  • Function of adult born neurons in memory formation during sleep, Symposium Speaker
    Sakaguchi M, Kumar D
    The 4th annual IIIS symposium, 2016, English, Tsukuba
    [Invited]

  • 成体脳に新生するニューロンの光制御により明らかにする,睡眠中の記憶形成機構
    Sakaguchi M
    比較記憶研究会, 2015, Japanese, 岡崎
    [Invited]

  • Brain regeneration
    Sakaguchi M
    慶應義塾大学眼科学講座定期セミナー, 2015, English
    [Invited]

  • The function of adult born neurons during sleep
    Sakaguchi M
    第 38 回日本神経科学大会, 2015, English, 神戸
    [Invited]

  • 光による睡眠ステージ特異的制御にて明らかにす る,新生ニューロンの記憶における機能
    Sakaguchi M
    成人病の病因・病態の解明に関する研究助成第 21 回研究発表会(TMFC), 2015, Japanese, 大阪
    [Invited]

  • Regeneration of neural circuits in the adult brain
    Sakaguchi M
    2014, English, Korea Advanced Institute of Science and Technology
    [Invited]

  • Manipulation of a traumatic memory, Symposium, Comprehensive Brain Science Network
    Sakaguchi M
    2014, English, Tokyo Medical and Dental University
    [Invited]

  • How memory engram is formed? (tentative)
    Sakaguchi M
    成体脳ニューロン新生 懇談会, 2014, English, 成体脳ニューロン新生 懇談会, University of Tokyo
    [Invited]

  • Function of adult neurogenesis in visual discrimination memory, Symposium on Behavioral Molecular Neuroscience
    Sakaguchi M
    2013, English, Yurakucho International Forum, Tokyo, Japan
    [Invited]

  • Neural stem cells, adult neurogenesis and memory: an overview of my past work and vision in IIIS
    Sakaguchi M
    2013, English, Epocal Tsukuba, Tsukuba, Japan
    [Invited]

  • IIIS における、光遺伝学を用いた、睡眠とその記憶における機能の研究について
    Sakaguchi M
    日本睡眠学会第 38 回定期学術集会, 2013, Japanese, 日本睡眠学会, Akita
    [Invited]

  • Selective and precise temporal ablation of adult born neurons in the hippocampus reveals their function in memory
    Sakaguchi M
    Neuroscience Institute department seminar, 2013, English, NeuroscienceInstitute, New York University
    [Invited]

■ Research Themes
  • Deciphering the mysteries of sleep:creating a global network of sleep neurobiologists
    柳沢 正史, 阿部 高志, 本城 咲季子, 林 悠, 史 蕭逸, 桜井 武, 坂口 昌徳, 坪田 有沙, ラザルス ミハエル, 斉藤 毅, Vogt Kaspar
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Fund for the Promotion of Joint International Research (International Leading Research ), University of Tsukuba, Dec. 2022 - Mar. 2029, Coinvestigator

  • Real-time motif detection from Calcium imaging
    手塚 太郎, 坂口 昌徳
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), University of Tsukuba, 01 Apr. 2024 - 31 Mar. 2027

  • Administration of "Manipulation of the Umwelt through the use of sound"
    善甫 啓一, 井野 敬子, 坂口 昌徳
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Transformative Research Areas (B), University of Tsukuba, 01 Apr. 2024 - 31 Mar. 2027

  • Function of fear memory retrieval during REM sleep
    坂口 昌徳, 橋本谷 祐輝
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), University of Tsukuba, 01 Apr. 2023 - 31 Mar. 2026
    本研究の目的は、レム睡眠中の恐怖記憶再想起の意義を解明することである。レム睡眠は夢を見る時期であり、覚醒時の恐怖体験が悪夢として再体験されることがある。この再体験時には、恐怖記憶をコードする特定のニューロン(記憶痕跡)が再活動するが、その意義は不明である。本研究では、この再活動の分析とレム睡眠中の操作を通じてその意義を明らかにする。 本年度は、特にカルシウムイメージングやAIを用いた技術でレム睡眠中の記憶再想起を詳細に分析する技術に大きな進展があった。

  • 睡眠中の音刺激による環世界マニピレーション
    坂口 昌徳
    日本学術振興会, 科学研究費助成事業, 学術変革領域研究(B), 筑波大学, Apr. 2024 - Mar. 2026, Principal investigator

  • 睡眠中の⾳刺激によるPTSDの新規治療法の開発
    坂口昌徳, 善甫啓一, 金吉晴, 北川博之, (株)S'UIMIN
    国立研究開発法人日本医療研究開発機構, 令和6年度「橋渡し研究プログラム」preF, May 2024 - Mar. 2025, Principal investigator
    Competitive research funding

  • Molecular Research and Treatment of Fear Memory in PTSD
    金 吉晴, 喜田 聡, 栗山 健一, 堀 弘明, 関口 敦, 坂口 昌徳
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A), Grant-in-Aid for Scientific Research (A), National Center of Neurology and Psychiatry, Apr. 2022 - Mar. 2025, Coinvestigator

  • 睡眠と冬眠:2つの「眠り」の解明と操作が拓く新世代医療の展開
    国立研究開発法人日本医療研究開発機構, ムーンショット型研究開発事業, 筑波大学国際統合睡眠医科学研究機構, Apr. 2020 - Mar. 2025, Coinvestigator

  • Elucidation of the mechanism by which adult-born neurons consolidate memories during sleep.
    坂口 昌徳, VERGARA GARCIA PABLO
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for JSPS Fellows, University of Tsukuba, 08 Mar. 2023 - 31 Mar. 2024
    成体期に新たなニューロンが生まれる数少ない領域である海馬歯状回に注目し、これらのニューロンの長期的な動態を探るための研究を行った。既存のカルシウムイメージング技術では、長期間にわたるニューロンの追跡が難しいため、新たな解析ツールCaliAli(Calcium Imaging Intersession Alignment)を開発した。 CaliAliは、長期実験におけるカルシウム信号を効率的に追跡・抽出するための包括的な解析パイプラインである。このツールは、カルシウムイメージングで得られる血管および神経構造を強調するフィルターを使用し、脳の整合性を修正する。また、長期間にわたる記録から生のデータを分離する特別なプロセスも備えている。さらに、バッチ処理を用いることで計算負荷を大幅に削減しつつ、高い性能を維持している。 CaliAliを用いた実験では、成体生まれのニューロンが文脈記憶の獲得後の睡眠段階で再活性化することを初めて示すことに成功した。これにより、記憶の統合におけるREM睡眠の重要性を新たに証明した。この成果は、CaliAliがニューロン追跡の新たな標準を設定し、神経ネットワークの進化と適応を長期にわたって研究する上で重要なツールとなることを示している。CaliAliのコードと論文はプレプリントとして公開されており、現在査読中である。

  • Study of the principles of consciousness
    坂口昌徳, 乘本裕明, 手塚太郎, 大西立顕
    Japan Agency for Medical Research and Development, Aug. 2021 - Mar. 2024, Principal investigator

  • Mechanisms of consciousness based on synchronous activity in the brain
    坂口昌徳
    The Uehara Memorial Foundation, Jan. 2021 - Mar. 2024, Principal investigator

  • Mechanisms of adult-born neurons for memory cosolidation in sleep
    坂口 昌徳
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for JSPS Fellows, University of Tsukuba, Sep. 2021 - Aug. 2023, Principal investigator

  • Function of synapse pruning in the regenerating memory circuit.
    坂口 昌徳
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Transformative Research Areas (A), University of Tsukuba, 10 Sep. 2021 - 31 Mar. 2023

  • Significance of synaptic plasticity for memory consolidation during sleep
    坂口 昌徳
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), University of Tsukuba, Apr. 2020 - Mar. 2023, Principal investigator
    通常、大人の脳では一度失われた神経細胞は再生されません。一方、海馬では、毎日一定数の神経細胞が再生されており、これを大人の脳では新生ニューロンと呼んでいます。新生ニューロンは、記憶において重要な働きをしています。一方で、記憶は睡眠の影響を強く受けます。かつては、睡眠中の新生ニューロンの働きはまったく知られていませんでした。特に、レム睡眠時に記憶を定着させる海馬ニューロンは特定されていませんでした。今回、超小型脳内視鏡を用いて、生きたマウスの脳内で新生ニューロンの活動を調べました。その結果、特に怖い体験をしたときに活性化した新生ニューロンが、その後のレム睡眠時に再活性化することを発見した。これは、レム睡眠時に夢を見る仕組みと関係があると考えられます。次に、レム睡眠時の新生ニューロンの活動の機能を理解するために、オプトジェネティクスを用いて、レム睡眠時のみ新生ニューロンの活動を人為的に操作する実験を行った。するとマウスは、あたかも怖い記憶を忘れたかのような行動をとった。さらに解析を進めると、これらの機能は特定の成長段階にある新生ニューロンに限られており、生まれたばかりの新生ニューロンや十分に成長した新生ニューロンでは同様の現象が見られないことがわかった。成人の脳にある新生ニューロンが、睡眠中に恐怖の記憶を定着させる仕組みを解明することで、脳の再生能力を高め、アルツハイマー病などの神経変性疾患や、PTSDなどの記憶処理に異常をきたす疾患の新たな治療法の開発につながることが期待されます。

  • Elucidation of the mechanism of memory fixation during sleep
    Goho Life Sciences International Fund, Dec. 2021 - Aug. 2022

  • レム睡眠中の記憶固定化におけるSRFの役割
    坂口 昌徳, SRINIVASAN SAKTHIVEL
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for JSPS Fellows, Grant-in-Aid for JSPS Fellows, University of Tsukuba, 08 Nov. 2019 - 31 Mar. 2022

  • Elucidation of pattern sepration mechanism based on new and old neruon interaction
    坂口昌徳
    公益財団法人三菱財団, 2022年度自然科学研究助成, Apr. 2021 - Mar. 2022, Principal investigator
    Others

  • Functional disruption of plastic neural circuits behind anxiety disorders
    Takeda Science Foundation, 生命科学研究助成, 筑波大学, Sep. 2021

  • Development and application of optical technology for spatiotemporal control of biological functions
    Masashi Yanagisawa
    JST, CREST, 2016 - 2021
    Competitive research funding

  • Sakaguchi Masanori
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B), Grant-in-Aid for Young Scientists (B), University of Tsukuba, Apr. 2016 - Mar. 2020
    Neurogenesis, the process by which new neurons are formed, takes place in the hippocampus throughout the lifespan of animals, including humans. At present, little is known about the contribution of ABNs to memory formation during sleep. In this project, we have revealed that adult-born neurons (ABNs) in the hippocampus, which is a brain region associated with memory, are responsible for memory consolidation during REM sleep. Our findings may lead to a deeper understanding of how memories are formed, retrieved, and consolidated, and could facilitate the development of new treatments for memory disorders using the self-regeneration potential of human brain.

  • Integration of the adult-born neurons into memory circuits during sleep
    坂口 昌徳, KUMAR DEEPENDRA
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for JSPS Fellows, Grant-in-Aid for JSPS Fellows, University of Tsukuba, 09 Nov. 2015 - 31 Mar. 2018
    睡眠の記憶に果たす役割は明解でない。また、成体脳で新生するニューロンが記憶の固定化に果たすメカニズムも明らかでない。我々のこれまでの研究から、成体の海馬で新生したニューロンが睡眠中に興奮することが、恐怖記憶の固定化に必須であることを示すデータが得られた。 そこで本研究を完成させるに当たり補助データを取得する過程で、幾つかの重要な知見が明らかになった。まず、恐怖記憶の固定化の過程を詳細に検討した所、恐怖学習から短い期間に、恐怖記憶の汎化が起こりやすいという事実が判明した。この事実に関し、単独でさらに掘り下げ、一つの論文として発表を行った。また、本課題の必須の要素技術である光遺伝学を使った恐怖記憶のリモートコントロール制御を完成させ論文発表を行った。これは本研究を発表する際に審査員の信用を得る上でも非常に重要と考えられる。さらに、睡眠中に新生ニューロンが果たす役割りについても検討を終了し、意外な表現形を発見した。 現在論文を完成させるために、柳沢正史博士をはじめとして内外の専門家から多くの意見を取り入れながら進めており、最終的な大きな成果へと繋がると考えられる。 現在、異る時期に生まれた新生ニューロンの機能差異、イメージングの最終実験を行っており、2016年度中の論文投稿を目指している。

  • Metabolome for sleep-dependent memory consolidation by adult-born neurons
    Takeda Science Foundation, Scholarship for Foreign Researchers, Apr. 2017 - Mar. 2018

  • 坂口昌徳
    MEXT, MEXT Scholarship for recruiting Msc. student, 2016 - 2018, Principal investigator
    Competitive research funding

  • 坂口昌徳
    The Tokyo Biochemical Research Foundation, 国際共同研究助成金, 2018, Principal investigator
    Competitive research funding

  • 坂口昌徳
    MEXT, MEXT Scholarship for recruiting Msc.student, 2016 - 2017, Principal investigator

  • 坂口昌徳
    Japan Foundation for Applied Enzymology, TMFC, 2013 - 2017, Principal investigator
    Competitive research funding

  • 坂口昌徳
    Takeda Science Foundation, Takeda Science Foundation Scholarship for Foreign Researchers, 2017, Principal investigator
    Competitive research funding

  • 睡眠中の新生ニュー ロンの活性化が記憶に及ぼす機能
    坂口 昌徳
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), University of Tsukuba, 01 Apr. 2014 - 31 Mar. 2016
    本年度、成体脳で新生するニューロンが記憶の固定化に果たすメカニズムも明らかにするために研究活動を行った。これまでの実験から、成体の海馬で新生したニューロンが睡眠中に興奮することが、恐怖記憶の固定化に必要であることが明らかになった。 そこで本研究を論文として完成させるに当たり、様々な追加・補助データを取得するべく実験を行った。その過程で、幾つかの意外かつ重要な結果が得られた。まず、光遺伝学を使って記憶の固定化と睡眠の関係を調べるための実験系を構築するに当たり、恐怖記憶の固定化の過程を詳細に検討した。すると恐怖学習課題から約6時間の期間に、記憶の汎化が起こり易い時間帯が有ることが明らかになった。この事実は、それだけでも重要な知見であると考え論文発表を行った。また、本課題を遂行する上で重要な要素技術である光遺伝学実験手法を用いることで、恐怖記憶のリモートコントロール制御を可能にする新しいトランスジェニックマウスが完成したため、それについての論文発表を行った。さらに、睡眠時期をより詳細に区別しながら実験していく中で、新生ニューロンが果たす役割りを詳細に検討し、驚くべき表現形を得た。 この様に幾つかの重要な成果や発見を得たため、当初に予定していたイメージングやシナプス定量については若干に計画を変更した点も有る。何れについても技術は完成し、現在データの取得を急いでいる。また論文をまとめるために、柳沢正史機構長をはじめとして内外の専門家から多くの意見を聞き入れ、今後大きな成果へと繋がると期待される。 現在、恐怖記憶以外の記憶に関しても、上記表現形が一般化できるか等の最終実験を行っており、2016年度中に新しい論文の投稿を目指している。

  • 坂口昌徳
    Research Foundation for Opto-Science and Technology, 研究助成金, 2015 - 2016, Principal investigator
    Competitive research funding

  • 坂口昌徳
    Kato Memorial Bioscience Foundation, 研究助成金, 2015 - 2016, Principal investigator
    Competitive research funding

  • 坂口昌徳
    Inamori Foundation, 研究助成金, 2016, Principal investigator
    Competitive research funding

  • 坂口昌徳
    The Ichiro Kanehara Foundation, Promotion of Medical Sciences and Medical Care, 2016, Principal investigator
    Competitive research funding

  • 坂口昌徳
    Senshin Medical Research Foundation, Senshin Medical Research Foundation Research Grant, 2016, Principal investigator
    Competitive research funding

  • 坂口昌徳
    Shimadzu Science Foundation, 研究助成金, 2016, Principal investigator
    Competitive research funding

  • 心的外傷後ストレス障害(PTSD)における記憶情報処理の病態生理
    坂口 昌徳
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), University of Tsukuba, 01 Apr. 2013 - 31 Mar. 2015
    本研究を遂行する過程において、予想外の発見が大きく分けて二つ有った。まず、トラウマ記憶の固定化過程における、記憶の汎化が起こりやすい期間の存在である。記憶の汎化とは、PTSDの患者に認められる主症状の一つで、トラウマ記憶と直接関係のない刺激が、トラウマ記憶と結びつき、それによって日常生活中の様々な刺激がトラウマ記憶を想起させてしまう。今回の研究で、トラウマ記憶学習から最低6時間、最長24時間の間に、最も汎化の起こりやすい時期があること、そして、汎化を起こす刺激は、新規のものでなく馴化が既に起こっている刺激である必要があることが明らかになった。この知見は、トラウマ後急性期にある患者の、汎化の予防等に役立つ知見を与えるものと考えられる(Fujinaka et al, in preparation)。次に、睡眠のトラウマ記憶における予想外の機能が明らかになった。我々は、トラウマ記憶の固定化の過程において、記憶を担うことが分かっている脳内の特定の神経回路だけを予期的に遺伝学的に追跡し、それらの細胞に光受容体を発現させ、人工的に操作可能とした。次に、それらの神経細胞に、各睡眠ステージ特異的に光照射を行うことで、睡眠の構造そのものを大きく変えることなく、トラウマ記憶を担う神経回路の、睡眠中の興奮を操作した。すると、予想外にも特定の睡眠ステージだけにおいて、それらの神経回路の興奮が、記憶の固定化に大きな役割を果たすことを見出した(未発表データ)。

  • 坂口昌徳
    FENS, FENS-JNS young researchers exchange support program, 2015, Principal investigator
    Competitive research funding

  • GSK財団: 研究助成金
    坂口昌徳
    GSK, GSK財団 Japan Research Grant, 2015, Principal investigator
    Competitive research funding

  • 坂口昌徳
    Kowa Life Science Foundation, Kowa Life Science Foundation Research Grant, 2015, Principal investigator
    Competitive research funding

  • 坂口昌徳
    Senshin Medical Research Foundation, Senshin Medical Research Foundation Research Grant, 2015, Principal investigator
    Competitive research funding

  • 坂口昌徳
    KANAE Foundation for the promotion of medical science, 研究助成金, 2015, Principal investigator
    Competitive research funding

  • 坂口昌徳
    Life Science Foundation of Japan, 研究助成金, 2015, Principal investigator
    Competitive research funding

  • 坂口昌徳
    The Uehara Memorial Foundation, The Uehara Memorial Foundation Research Grant, 2015, Principal investigator
    Competitive research funding

  • Memory transfer across neural networks
    SAKAGUCHI MASANORI
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B), Grant-in-Aid for Young Scientists (B), University of Tsukuba, 01 Apr. 2012 - 31 Mar. 2014
    To provide evidence that memory transfers across neuronal networks, the following three attempts were made: 1.) inducing expression of target genes in the neuronal circuit which encodes memory, 2.) tracing brain areas where the above neuronal circuit projects its axons, and 3.) manipulating the aforementioned neuronal circuits. For the first attempt, it was proven difficult to induce the neuronal circuit in the hippocampus to encode memory by CREB gene overexpression. Therefore, a new approach to artificially induce memory encoding by optogenetics has been carried out (unpublished results). Since it was deemed problematic to utilize WGA-Cre for the purpose of the second attempt, a new approach utilizing VSV has been undertaken. Finally, the ontogenetic technique was established in the third attempt which produced some usable data.

  • 坂口昌徳
    Brain Science Foundation, Research Grant, 2013, Principal investigator
    Competitive research funding

  • 坂口昌徳
    Research Foundation for Opto-science and Technology, 研究助成金, 2011 - 2012, Principal investigator
    Competitive research funding

  • 坂口昌徳
    Japanese Society for the Promotion of Science, Postdoctoral Fellowship, Japanese Society for the Promotion of Science, (2yrs. salary), 2009 - 2011, Principal investigator
    Competitive research funding

  • 坂口昌徳
    Takeda Science Foundation, Takeda Science Foundation Research Grant, 2011, Principal investigator
    Competitive research funding

  • Uehara Memorial Foundation
    坂口昌徳
    Uehara Memorial Foundation, 研究奨励金, 2011, Principal investigator
    Competitive research funding

  • 坂口昌徳
    Japanese Society for the Promotion of Science, Travel Grant for attending Lindau Nobel Laureates Meetings, Japanese Society for the Promotion of Science, (travel expense and attending fee)?, 2010, Principal investigator
    Competitive research funding

  • 坂口昌徳
    RIKEN, RIKEN Seeds Fund, Research Grant, 2010, Principal investigator
    Competitive research funding

  • 坂口昌徳
    The Hospital for Sick Children, RESTRACOMP postdoctoral fellowship, The Hospital for Sick Children, (2yrs. salary), 2007 - 2008, Principal investigator
    Competitive research funding

  • 成体中枢神経幹細胞における糖鎖分子の機能解析
    坂口 昌徳
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (Start-up), Grant-in-Aid for Young Scientists (Start-up), Keio University, 2006 - 2007
    我々は、本年度、Galectin-1が成体の神経幹細胞の増殖を制御することを明らかにした(Sakaguchi et al.,PNAS,2006)。また、本知見を利用して実際に脳梗塞モデル動物においてGalectin-1を治療方法として利用できる事を証明した(論文投稿中)。しかしながら、その作用メカニズムに関しては不明な点が残った。そこで、Galectin-1の結合する分子を明らかにするために、神経幹細胞およびその周囲組織でGalectin-1と結合する分子を探索した。その過程で、Galectin-1がbeta1IntegrinおよびATPIa3という分子に結合する可能性が示唆された。すなわち、Galectin-1リコンビナントタンパク質をカラムに固定化し、神経幹細胞とその周囲組織の破砕物をカラムに反応させることで、Galectni-1と結合する分子を分離・濃縮した。結果的に、beta1IntegrinおよびATP1a3という分子に結合する可能性が示唆された。次に、それらの分子の発現パターンについて詳細な解析を行った。beta1Ingetginは神経幹細胞および神経前駆細胞の一部に、Atp1a3は脳室上衣細胞に発現していた(投稿準備中)。本研究は、これまで不明であった神経幹細胞周囲組織(ニッチ)において神経幹細胞の増殖を制御する分子の機能解明に貢献するという点で重要と考えられる。また、成体の神経幹細胞は、側脳室周囲と海馬の2つの場所に存在しているが、今回我々は新たに、海馬の神経幹細胞においてもGalectin-1の機能的重要性を示唆するデータを得た。海馬は記憶・学習において重要な臓器である。今後、本研究を推進することで、成体海馬の神経新生の分子メカニズムについて、新たな一面を明らかにできる可能性がある。

  • 坂口昌徳
    The Naito Foundation, Naito foundation research grant,, 2005, Principal investigator
    Competitive research funding

  • 坂口昌徳
    MEXT, High-tech research center improvement project of Japan Ministry of Education, Culture, Sports and Technology, 2005, Principal investigator
    Competitive research funding

  • 坂口昌徳
    NIH, Keystone Symposia Scholarship Award, (NIH grant; 1R13 NS047606-01),, 2004, Principal investigator
    Competitive research funding

■ Industrial Property Rights
  • トラウマ音刺激の作成方法
    坂口昌徳, 金吉晴, 善甫啓一, 井野敬子
    特願2026-027927, 24 Feb. 2026, 神戸大学
    Patent right

  • 細胞統合促進システム
    坂口昌徳, 小柳伊代, 永井一稀
    特願2025-089783, 29 May 2025, 筑波大学
    Patent right

  • データ提供装置、データ提供方法及びコンピュータープログラム
    善甫 啓一, 山内 由大, 坂口昌徳
    特願2023-209641/PCT/JP2024/044030, 12 Dec. 2023, 筑波大学
    Patent right

  • 判定装置、光照射装置、及びプログラム
    坂口 昌徳, 手塚太郎
    特願2019-145967, 08 Aug. 2019, 特許第07321511号, 28 Jul. 2023
    Patent right

  • 小型撮像装置
    坂口 昌徳, 手塚太郎, 細川拓馬
    特願2019-137229, 25 Jul. 2019, 特許第7299610号, 20 Jun. 2023
    Patent right

  • Agent for inhibiting proliferation of neural stem cells.
    Okano H, Sakaguchi M, Hirabayashi J, Sawamoto K
    2007, US 20070248592A1, 2007
    Patent right

  • Methods for enhancing survival and/or proliferation of neural stem cells and neurite extension enhancers therefore pharmaceutical compositions containing neural stem cells assay methods and screening methods.
    Okano H, Okano JH, Sakaguchi M, Mizusawa H, Ishibashi S
    PCT/PO4/13043, 2004, US 200700.98701A1, 2007
    Patent right

  • Method of promoting subsistence and/or proliferation of neural stem cell and promoting extension of neurite, promoter therefor, pharmaceutical composition containing neural stem cell, method of assay and method of screening
    Ishibashi S, Mizusawa H, Okano H, Okano JH, Sakaguchi M
    PCT/JP2004/0113043, 2004, WO2005026343A1, 2005
    Patent right

  • Method of inducing growth of nerve stem cells.
    Toda M, Okano H, Kawakami Y, Toyama Y, Mikami Y, Sakaguchi M
    PCT/JP03/03868, 2003, US 20050226852A1, 2005
    Patent right

■ Social Contribution Activities
  • UCLAminiscopeProductionSupport
    Masanori Sakaguchi
    http://sakaguchi-miniscope.blogspot.com/, Jan. 2018

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