Pub Date : 2025-11-20DOI: 10.1038/s41593-025-02138-3
{"title":"Tau pathology in mouse spinal neurons underlies early touch loss and heralds cognitive decline.","authors":"","doi":"10.1038/s41593-025-02138-3","DOIUrl":"https://doi.org/10.1038/s41593-025-02138-3","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"107 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-19DOI: 10.1038/s41593-025-02172-1
Erica Korb, Carol L. Wilkinson, Ryan N. Delgado, Kathryn L. Lovero, Steven Finkbeiner
{"title":"Author Correction: Arc in the nucleus regulates PML-dependent GluA1 transcription and homeostatic plasticity","authors":"Erica Korb, Carol L. Wilkinson, Ryan N. Delgado, Kathryn L. Lovero, Steven Finkbeiner","doi":"10.1038/s41593-025-02172-1","DOIUrl":"10.1038/s41593-025-02172-1","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 12","pages":"2646-2646"},"PeriodicalIF":20.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41593-025-02172-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145545463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-18DOI: 10.1038/s41593-025-02116-9
Miguel Vivar-Lazo, Christopher R. Fetsch
{"title":"Neural basis of concurrent deliberation toward a choice and confidence judgment","authors":"Miguel Vivar-Lazo, Christopher R. Fetsch","doi":"10.1038/s41593-025-02116-9","DOIUrl":"https://doi.org/10.1038/s41593-025-02116-9","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"129 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145536184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-18DOI: 10.1038/s41593-025-02176-x
Dongwon Choi, Eunkyung Park, Joshua Choi, Renhao Lu, Jin Suh Yu, Chiyoon Kim, Luping Zhao, James Yu, Brandon Nakashima, Sunju Lee, Dhruv Singhal, Joshua P. Scallan, Bin Zhou, Chester J. Koh, Esak Lee, Young-Kwon Hong
Pub Date : 2025-11-18DOI: 10.1038/s41593-025-02114-x
Ziyue Aiden Wang, Balint Kurgyis, Susu Chen, Byungwoo Kang, Feng Chen, Yi Liu, Dave Liu, Karel Svoboda, Nuo Li, Shaul Druckmann
Movement-related activity has been detected across much of the brain, including sensory and motor regions. However, much remains unknown regarding the distribution of movement-related activity across brain regions, and how this activity relates to neural computation. Here we analyzed movement-related activity in brain-wide recordings of more than 50,000 neurons in mice performing a decision-making task. We used multiple machine learning methods to predict neural activity from videography and found that movement-related signals differed across areas, with stronger movement signals close to the motor periphery and in motor-associated subregions. Delineating activity that predicts or follows movement revealed fine-scale structure of sensory and motor encoding across and within brain areas. Through single-trial video-based predictions of behavior, we identified activity modulation by uninstructed movements and their impact on choice-related activity analysis. Our work provides a map of movement encoding across the brain and approaches for linking neural activity, uninstructed movements and decision-making.
{"title":"Brain-wide analysis reveals movement encoding structured across and within brain areas","authors":"Ziyue Aiden Wang, Balint Kurgyis, Susu Chen, Byungwoo Kang, Feng Chen, Yi Liu, Dave Liu, Karel Svoboda, Nuo Li, Shaul Druckmann","doi":"10.1038/s41593-025-02114-x","DOIUrl":"https://doi.org/10.1038/s41593-025-02114-x","url":null,"abstract":"Movement-related activity has been detected across much of the brain, including sensory and motor regions. However, much remains unknown regarding the distribution of movement-related activity across brain regions, and how this activity relates to neural computation. Here we analyzed movement-related activity in brain-wide recordings of more than 50,000 neurons in mice performing a decision-making task. We used multiple machine learning methods to predict neural activity from videography and found that movement-related signals differed across areas, with stronger movement signals close to the motor periphery and in motor-associated subregions. Delineating activity that predicts or follows movement revealed fine-scale structure of sensory and motor encoding across and within brain areas. Through single-trial video-based predictions of behavior, we identified activity modulation by uninstructed movements and their impact on choice-related activity analysis. Our work provides a map of movement encoding across the brain and approaches for linking neural activity, uninstructed movements and decision-making.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145536221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-18DOI: 10.1038/s41593-025-02171-2
Katya J. Park, Carlos Ayala Grosso, Isabelle Aubert, David R. Kaplan, Freda D. Miller
{"title":"Author Correction: p75NTR-dependent, myelin-mediated axonal degeneration regulates neural connectivity in the adult brain","authors":"Katya J. Park, Carlos Ayala Grosso, Isabelle Aubert, David R. Kaplan, Freda D. Miller","doi":"10.1038/s41593-025-02171-2","DOIUrl":"10.1038/s41593-025-02171-2","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 12","pages":"2646-2646"},"PeriodicalIF":20.0,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41593-025-02171-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145536182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-18DOI: 10.1038/s41593-025-02097-9
Christian Lüscher, Valentina Emiliani, Nita Farahany, Aryn Gittis, Viviana Gradinaru, Katherine A. High, Botond Roska, José-Alain Sahel, Ofer Yizhar, Hongkui Zeng, Karl Deisseroth
Optogenetics has transformed basic research on neural circuitry, led to diverse experimental insights into human brain function and dysfunction, and opened pathways for clinical translation based on new understanding of how specific cell types contribute to cognition and behavior. Many of these translational pathways do not rely on the direct application of optogenetics in humans, but rather develop and advance other treatment modalities by leveraging causal knowledge derived from optogenetic circuit neuroscience. However, a recent proof-of-principle study—showing that optogenetics applied directly to the human central nervous system can treat blindness—underscores not only the curative potential but also the need for careful ethical consideration in the extension of direct optogenetic intervention to other disorders. Here, we review relevant considerations—including the selection of clinical indications, identification of molecular and optical strategies for specificity, and navigation of safety and regulatory issues—that together inform the development of optogenetic translation targeting cells and circuits that have been causally implicated through optogenetic discoveries. This Perspective discusses the challenges involved in translating optogenetic research into clinical practice, including clinical and pragmatic choices, potential toxicity and immune responses, regulatory issues and ethical considerations.
{"title":"Roadmap for direct and indirect translation of optogenetics into discoveries and therapies for humans","authors":"Christian Lüscher, Valentina Emiliani, Nita Farahany, Aryn Gittis, Viviana Gradinaru, Katherine A. High, Botond Roska, José-Alain Sahel, Ofer Yizhar, Hongkui Zeng, Karl Deisseroth","doi":"10.1038/s41593-025-02097-9","DOIUrl":"10.1038/s41593-025-02097-9","url":null,"abstract":"Optogenetics has transformed basic research on neural circuitry, led to diverse experimental insights into human brain function and dysfunction, and opened pathways for clinical translation based on new understanding of how specific cell types contribute to cognition and behavior. Many of these translational pathways do not rely on the direct application of optogenetics in humans, but rather develop and advance other treatment modalities by leveraging causal knowledge derived from optogenetic circuit neuroscience. However, a recent proof-of-principle study—showing that optogenetics applied directly to the human central nervous system can treat blindness—underscores not only the curative potential but also the need for careful ethical consideration in the extension of direct optogenetic intervention to other disorders. Here, we review relevant considerations—including the selection of clinical indications, identification of molecular and optical strategies for specificity, and navigation of safety and regulatory issues—that together inform the development of optogenetic translation targeting cells and circuits that have been causally implicated through optogenetic discoveries. This Perspective discusses the challenges involved in translating optogenetic research into clinical practice, including clinical and pragmatic choices, potential toxicity and immune responses, regulatory issues and ethical considerations.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 12","pages":"2415-2431"},"PeriodicalIF":20.0,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41593-025-02097-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145545361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-17DOI: 10.1038/s41593-025-02100-3
Chao Zheng, Bastien Hervé, Mandy Meijer, Leslie Ann Rubio Rodríguez-Kirby, André Ortlieb Guerreiro Cacais, Petra Kukanja, Mukund Kabbe, Tony Jimenez-Beristain, Tomas Olsson, Eneritz Agirre, Gonçalo Castelo-Branco
Multiple sclerosis (MS) is a chronic autoimmune disease that targets mature oligodendrocytes (MOLs) and their myelin. MOLs are heterogeneous and can transition to immune-like states in MS. However, the dynamics of this process remain unclear. Here, we used single-cell multiome assay for transposase-accessible chromatin and RNA sequencing targeting oligodendroglia (OLG) from the experimental autoimmune encephalomyelitis (EAE) MS mouse model at multiple disease stages. We found that immune OLG states appear at early disease stages and persist to late stages, which can be consistent with epigenetic memory of previous neuroinflammation. Transcription factor activity suggested immunosuppression in OLG at early disease stages. Different MOLs exhibit differential responsiveness to EAE, with MOL2 exhibiting a stronger transcriptional immune response than MOL5/MOL6, and showed divergent responses at the epigenetic level during disease evolution. Our single-cell multiomic resource highlights dynamic and subtype-specific responses of OLG to EAE, which might be amenable to modulation in MS. Single-cell ATAC/RNA multiomic profiling was used to investigate how oligodendrocyte lineage cells respond across multiple disease stages within a mouse MS model, revealing early activation of immune genes along with oligodendrocyte subtype-specific responses.
{"title":"Distinct transcriptomic and epigenomic responses of mature oligodendrocytes during disease progression in a mouse model of multiple sclerosis","authors":"Chao Zheng, Bastien Hervé, Mandy Meijer, Leslie Ann Rubio Rodríguez-Kirby, André Ortlieb Guerreiro Cacais, Petra Kukanja, Mukund Kabbe, Tony Jimenez-Beristain, Tomas Olsson, Eneritz Agirre, Gonçalo Castelo-Branco","doi":"10.1038/s41593-025-02100-3","DOIUrl":"10.1038/s41593-025-02100-3","url":null,"abstract":"Multiple sclerosis (MS) is a chronic autoimmune disease that targets mature oligodendrocytes (MOLs) and their myelin. MOLs are heterogeneous and can transition to immune-like states in MS. However, the dynamics of this process remain unclear. Here, we used single-cell multiome assay for transposase-accessible chromatin and RNA sequencing targeting oligodendroglia (OLG) from the experimental autoimmune encephalomyelitis (EAE) MS mouse model at multiple disease stages. We found that immune OLG states appear at early disease stages and persist to late stages, which can be consistent with epigenetic memory of previous neuroinflammation. Transcription factor activity suggested immunosuppression in OLG at early disease stages. Different MOLs exhibit differential responsiveness to EAE, with MOL2 exhibiting a stronger transcriptional immune response than MOL5/MOL6, and showed divergent responses at the epigenetic level during disease evolution. Our single-cell multiomic resource highlights dynamic and subtype-specific responses of OLG to EAE, which might be amenable to modulation in MS. Single-cell ATAC/RNA multiomic profiling was used to investigate how oligodendrocyte lineage cells respond across multiple disease stages within a mouse MS model, revealing early activation of immune genes along with oligodendrocyte subtype-specific responses.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 12","pages":"2612-2627"},"PeriodicalIF":20.0,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41593-025-02100-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-13DOI: 10.1038/s41593-025-02170-3
Abhishek Dubey, Erika Yamashita, Biljana Stangeland, Imane Abbas, David Fooksman, Robert A. Harris, Gregory M. Palmer, Wade R. Koba, Jinghang Zhang, Benjamin T. Himes, Olivia R. Lu, Winson S. Ho, Raoul V. Kuiper, Derek Huffman, Zhiping Wu, Yutaka Uchida, Masaru Ishii, Rachel L. Welch, Alexander F. Fiedler, David Reynolds, S. A. Mohieb Hosainey, Kostantin Dobrenis, Qinge Ye, Kevin Fisher, Nathaniel Killian, E. Richard Stanley, Emad Eskandar, Jinan Behnan
{"title":"Author Correction: Brain tumors induce widespread disruption of calvarial bone and alteration of skull marrow immune landscape","authors":"Abhishek Dubey, Erika Yamashita, Biljana Stangeland, Imane Abbas, David Fooksman, Robert A. Harris, Gregory M. Palmer, Wade R. Koba, Jinghang Zhang, Benjamin T. Himes, Olivia R. Lu, Winson S. Ho, Raoul V. Kuiper, Derek Huffman, Zhiping Wu, Yutaka Uchida, Masaru Ishii, Rachel L. Welch, Alexander F. Fiedler, David Reynolds, S. A. Mohieb Hosainey, Kostantin Dobrenis, Qinge Ye, Kevin Fisher, Nathaniel Killian, E. Richard Stanley, Emad Eskandar, Jinan Behnan","doi":"10.1038/s41593-025-02170-3","DOIUrl":"10.1038/s41593-025-02170-3","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 12","pages":"2645-2645"},"PeriodicalIF":20.0,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41593-025-02170-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145498279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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