Pub Date : 2025-12-03DOI: 10.1038/s41593-025-02181-0
Nature Neuroscience has introduced two initiatives to promote the quality, transparency and inclusivity of peer review. One enables the publication of peer review reports and authors’ responses, and the other facilitates the participation of early career researchers.
{"title":"Enhancing peer review at Nature Neuroscience","authors":"","doi":"10.1038/s41593-025-02181-0","DOIUrl":"10.1038/s41593-025-02181-0","url":null,"abstract":"Nature Neuroscience has introduced two initiatives to promote the quality, transparency and inclusivity of peer review. One enables the publication of peer review reports and authors’ responses, and the other facilitates the participation of early career researchers.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 12","pages":"2403-2403"},"PeriodicalIF":20.0,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41593-025-02181-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659790","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 : 2025-12-03DOI: 10.1038/s41593-025-02178-9
William P. Olson
{"title":"Recurrence has it covered","authors":"William P. Olson","doi":"10.1038/s41593-025-02178-9","DOIUrl":"10.1038/s41593-025-02178-9","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 12","pages":"2406-2406"},"PeriodicalIF":20.0,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659784","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}
Enhancer elements direct cell-type-specific gene expression programs. After injury, cells change their transcriptional state to adapt to stress and initiate repair. Here we investigate how injury-induced transcriptional programs are encoded within enhancers in the mammalian CNS. Leveraging single-nucleus transcriptomics and chromatin accessibility profiling, we identify thousands of injury-induced, cell-type-specific enhancers in the mouse spinal cord after a contusion injury. These are abundant in glial cells and retain cell-type specificity, even when regulating shared wound response genes. By modeling glial injury-responsive enhancers using deep learning, we reveal that their architecture encodes cell-type specificity by integrating generic stimulus response elements with cell identity programs. Finally, through in vivo enhancer screening, we demonstrate that injury-responsive enhancers can selectively target reactive astrocytes across the CNS using therapeutically relevant gene delivery vectors. Our decoding of the principles of injury-responsive enhancers enables the design of sequences that can be programmed to target disease-associated cell states.
{"title":"The regulatory code of injury-responsive enhancers enables precision cell-state targeting in the CNS.","authors":"Margherita Zamboni,Adrián Martínez-Martín,Gabriel Rydholm,Timm Häneke,Laura Pintado Almeida,Deniz Seçilmiş,Christoph Ziegenhain,Enric Llorens-Bobadilla","doi":"10.1038/s41593-025-02131-w","DOIUrl":"https://doi.org/10.1038/s41593-025-02131-w","url":null,"abstract":"Enhancer elements direct cell-type-specific gene expression programs. After injury, cells change their transcriptional state to adapt to stress and initiate repair. Here we investigate how injury-induced transcriptional programs are encoded within enhancers in the mammalian CNS. Leveraging single-nucleus transcriptomics and chromatin accessibility profiling, we identify thousands of injury-induced, cell-type-specific enhancers in the mouse spinal cord after a contusion injury. These are abundant in glial cells and retain cell-type specificity, even when regulating shared wound response genes. By modeling glial injury-responsive enhancers using deep learning, we reveal that their architecture encodes cell-type specificity by integrating generic stimulus response elements with cell identity programs. Finally, through in vivo enhancer screening, we demonstrate that injury-responsive enhancers can selectively target reactive astrocytes across the CNS using therapeutically relevant gene delivery vectors. Our decoding of the principles of injury-responsive enhancers enables the design of sequences that can be programmed to target disease-associated cell states.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"6 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145656995","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 : 2025-12-02DOI: 10.1038/s41593-025-02160-5
Kianoush Banaie Boroujeni,Randolph F Helfrich,Ian C Fiebelkorn,J Nicole Bentley,Peter Brunner,Jack J Lin,Robert T Knight,Sabine Kastner
Brain-wide communication supporting flexible behavior requires coordination between sensory and associative regions but how brain networks route sensory information at fast timescales to guide action remains unclear. Using human intracranial electrophysiology and spiking neural networks during spatial attention tasks, where participants detected targets at cued locations, we show that high-frequency activity bursts (HFAbs) mark temporal windows of elevated population firing that enable fast, long-range communications. HFAbs were evoked by sensory cues and targets, dynamically coupled to low-frequency rhythms. Notably, both the strength of cue-evoked HFAbs and their decoupling from slow rhythms predicted behavioral accuracy. HFAbs synchronized across the brain, revealing distinct cue- and target-activated subnetworks. These subnetworks exhibited lead-lag dynamics following target onset, with cue-activated subnetworks preceding target-activated subnetworks when cues were informative. Computational modeling suggested that HFAbs reflect transitions to population spiking, denoting temporal windows for network communications supporting attentional performance. These findings establish HFAbs as signatures of population state transitions, supporting information routing across distributed brain networks.
{"title":"High-frequency bursts facilitate fast communication for human spatial attention.","authors":"Kianoush Banaie Boroujeni,Randolph F Helfrich,Ian C Fiebelkorn,J Nicole Bentley,Peter Brunner,Jack J Lin,Robert T Knight,Sabine Kastner","doi":"10.1038/s41593-025-02160-5","DOIUrl":"https://doi.org/10.1038/s41593-025-02160-5","url":null,"abstract":"Brain-wide communication supporting flexible behavior requires coordination between sensory and associative regions but how brain networks route sensory information at fast timescales to guide action remains unclear. Using human intracranial electrophysiology and spiking neural networks during spatial attention tasks, where participants detected targets at cued locations, we show that high-frequency activity bursts (HFAbs) mark temporal windows of elevated population firing that enable fast, long-range communications. HFAbs were evoked by sensory cues and targets, dynamically coupled to low-frequency rhythms. Notably, both the strength of cue-evoked HFAbs and their decoupling from slow rhythms predicted behavioral accuracy. HFAbs synchronized across the brain, revealing distinct cue- and target-activated subnetworks. These subnetworks exhibited lead-lag dynamics following target onset, with cue-activated subnetworks preceding target-activated subnetworks when cues were informative. Computational modeling suggested that HFAbs reflect transitions to population spiking, denoting temporal windows for network communications supporting attentional performance. These findings establish HFAbs as signatures of population state transitions, supporting information routing across distributed brain networks.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"244 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145656991","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 : 2025-12-01DOI: 10.1038/s41593-025-02113-y
Ruoqi Yu, Brian M. Lozinski, Ally Seifert, Khanh Ta, Stephanie Zandee, Deepak K. Kaushik, Jian Park, Wendy Klement, Sandra Larouche, Sotirios Tsimikas, Joseph L. Witztum, Dorian B. McGavern, Alexandre Prat, Yifei Dong
{"title":"Oxidized phosphatidylcholines deposition drives chronic neurodegeneration in a mouse model of progressive multiple sclerosis via IL-1β signaling","authors":"Ruoqi Yu, Brian M. Lozinski, Ally Seifert, Khanh Ta, Stephanie Zandee, Deepak K. Kaushik, Jian Park, Wendy Klement, Sandra Larouche, Sotirios Tsimikas, Joseph L. Witztum, Dorian B. McGavern, Alexandre Prat, Yifei Dong","doi":"10.1038/s41593-025-02113-y","DOIUrl":"https://doi.org/10.1038/s41593-025-02113-y","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"25 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645167","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 : 2025-11-27DOI: 10.1038/s41593-025-02124-9
Christian Waiblinger, April R. Reedy, Garrett B. Stanley
{"title":"An adaptive and flexible role for primary sensory cortex","authors":"Christian Waiblinger, April R. Reedy, Garrett B. Stanley","doi":"10.1038/s41593-025-02124-9","DOIUrl":"https://doi.org/10.1038/s41593-025-02124-9","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"20 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609482","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 : 2025-11-26DOI: 10.1038/s41593-025-02149-0
Heidi McAlpine, Marius Rosier, Jordan Rozario, Xiaoyu Wang, Verena C. Wimmer, Robertas Guzulaitis, Hefei Guan, Yi Hu, Leonid Chirlov, Christian Davey, Sue Finch, Katharine Jann Drummond, Lucy Maree Palmer
{"title":"Increased neural excitability and glioma synaptic activity drives glioma proliferation in human cortex","authors":"Heidi McAlpine, Marius Rosier, Jordan Rozario, Xiaoyu Wang, Verena C. Wimmer, Robertas Guzulaitis, Hefei Guan, Yi Hu, Leonid Chirlov, Christian Davey, Sue Finch, Katharine Jann Drummond, Lucy Maree Palmer","doi":"10.1038/s41593-025-02149-0","DOIUrl":"https://doi.org/10.1038/s41593-025-02149-0","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"17 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599442","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 : 2025-11-25DOI: 10.1038/s41593-025-02182-z
Ya’el Courtney, Joshua P. Head, Neil Dani, Olga V. Chechneva, Frederick B. Shipley, Yong Zhang, Michael J. Holtzman, Cameron Sadegh, Towia A. Libermann, Maria K. Lehtinen
{"title":"Author Correction: Choroid plexus apocrine secretion shapes CSF proteome during mouse brain development","authors":"Ya’el Courtney, Joshua P. Head, Neil Dani, Olga V. Chechneva, Frederick B. Shipley, Yong Zhang, Michael J. Holtzman, Cameron Sadegh, Towia A. Libermann, Maria K. Lehtinen","doi":"10.1038/s41593-025-02182-z","DOIUrl":"https://doi.org/10.1038/s41593-025-02182-z","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"90 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145594097","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}
Genome-wide association studies (GWASs) of bipolar disorder (BD) have predominantly included individuals of European (EUR) ancestry, underrepresenting non-EUR populations and limiting insight into disease mechanisms. Here we performed a GWAS of BD in Han Chinese individuals (5,164 cases and 13,460 controls) and conducted comparative and integrative analyses with independent East Asian (EAS, 4,479 cases and 75,725 controls) and EUR (59,287 cases and 781,022 controls) cohorts from the PGC4 GWAS. Our GWAS in EAS ancestry identified two genome-wide significant risk loci, including variants at the major histocompatibility complex (MHC) class II region. Incorporating EAS data into trans-ancestry GWAS revealed 93 significant loci (23 novel). Heritability enrichment analyses implicated a variety of neuronal cell types. Multidimensional post-GWAS prioritization identified 39 high-confidence risk genes, of which 15 were differentially expressed in the brains of patients with BD, 12 modulated BD-relevant behaviors in mice and 18 are pharmacologically tractable. This work advances understanding of the biological underpinnings of BD and provides direction for future research in underrepresented populations.
{"title":"Trans-ancestry genome-wide analyses of bipolar disorder in East Asian and European populations improve genetic discovery.","authors":"Chu-Yi Zhang,Miao Li,Ping Sun,Li Hui,Yuan Gao,Jian-Zhong Yang,Nan Zhang,Xiaoyang Feng,Yong Wu,Lei Guo,Jing Yuan,Hong-Yan Jiang,Yu-Qi Cheng,Simeng Ma,Qian Gong,Yaoyao Sun,Yi Li,Na Qu,Xu-Yuan Yin,Lu Wang,Yongfeng Yang,Chuansheng Wang,Luxian Lv,Dongsheng Zhou,Xingxing Li,Xiaogang Chen,Chen Zhang,Jun Chen,Xueqin Song,Jinsong Tang,Jun Cai,Weixing Fan,Wei Tang,Wenxin Tang,Wenqiang Li,Xia Tang,Xiaoxi Zhang,Yan Lu,Yong-Gang Yao,Chuang Wang,Hon-Cheong So,Nakao Iwata,Masashi Ikeda,Takeo Saito,Zhongchun Liu,Shuahua Xu,Weihua Yue, ,Yiru Fang,Feng Zhu,Xiao Xiao,Ming Li","doi":"10.1038/s41593-025-02147-2","DOIUrl":"https://doi.org/10.1038/s41593-025-02147-2","url":null,"abstract":"Genome-wide association studies (GWASs) of bipolar disorder (BD) have predominantly included individuals of European (EUR) ancestry, underrepresenting non-EUR populations and limiting insight into disease mechanisms. Here we performed a GWAS of BD in Han Chinese individuals (5,164 cases and 13,460 controls) and conducted comparative and integrative analyses with independent East Asian (EAS, 4,479 cases and 75,725 controls) and EUR (59,287 cases and 781,022 controls) cohorts from the PGC4 GWAS. Our GWAS in EAS ancestry identified two genome-wide significant risk loci, including variants at the major histocompatibility complex (MHC) class II region. Incorporating EAS data into trans-ancestry GWAS revealed 93 significant loci (23 novel). Heritability enrichment analyses implicated a variety of neuronal cell types. Multidimensional post-GWAS prioritization identified 39 high-confidence risk genes, of which 15 were differentially expressed in the brains of patients with BD, 12 modulated BD-relevant behaviors in mice and 18 are pharmacologically tractable. This work advances understanding of the biological underpinnings of BD and provides direction for future research in underrepresented populations.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"2 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599914","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}
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