Pub Date : 2025-12-03DOI: 10.1038/s41593-025-02177-w
Ioana A. Marin
{"title":"When protein turns toxic","authors":"Ioana A. Marin","doi":"10.1038/s41593-025-02177-w","DOIUrl":"10.1038/s41593-025-02177-w","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":"145659783","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 : 2025-12-03DOI: 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}
Pub Date : 2025-12-02DOI: 10.1038/s41593-025-02131-w
Margherita Zamboni, Adrián Martínez-Martín, Gabriel Rydholm, Timm Häneke, Laura Pintado Almeida, Deniz Seçilmiş, Christoph Ziegenhain, Enric Llorens-Bobadilla
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. Zamboni et al. reveal how enhancers encode cell-type-specific responses to CNS injury. By combining multiomic profiling, deep learning and in vivo screening, they uncover injury-responsive enhancer logic and enable targeting of reactive astrocytes.
{"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":"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. Zamboni et al. reveal how enhancers encode cell-type-specific responses to CNS injury. By combining multiomic profiling, deep learning and in vivo screening, they uncover injury-responsive enhancer logic and enable targeting of reactive astrocytes.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"29 2","pages":"337-349"},"PeriodicalIF":20.0,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41593-025-02131-w.pdf","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":"OA","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. Using intracranial electroencephalography from patients with epilepsy during spatial attention tasks, this study shows that high-frequency bursts facilitate fast communications in brain networks and support attentional information routing.
{"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":"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. Using intracranial electroencephalography from patients with epilepsy during spatial attention tasks, this study shows that high-frequency bursts facilitate fast communications in brain networks and support attentional information routing.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"29 2","pages":"435-444"},"PeriodicalIF":20.0,"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
Oxidized phosphatidylcholines (OxPCs) are neurotoxic byproducts of oxidative stress elevated in the central nervous system (CNS) during progressive multiple sclerosis (P-MS). How OxPCs contribute to the pathophysiology of P-MS is unclear. Here we show that stereotactic OxPC deposition in the CNS of mice induces a chronic compartmentalized lesion with pathological features similar to chronic active lesions found in P-MS. Using this model, we found that although microglia protected the CNS from chronic neurodegeneration, they were also replaced by monocyte-derived macrophages in chronic OxPC lesions. Aging, a risk factor for P-MS, altered microglial composition and exacerbated neurodegeneration in chronic OxPC lesions. Amelioration of disease pathology in Casp1/Casp4-deficient mice and by blockade of IL-1R1 indicate that IL-1β signaling contributes to chronic OxPC accumulation and neurodegeneration. These results highlight OxPCs and IL-1β as potential drivers of chronic neurodegeneration in MS and suggest that their neutralization could be effective for treating P-MS. In this study, Yu et al. found that a positive feedback loop between oxidized phosphatidylcholine and IL-1β promotes chronic neurodegeneration in the central nervous system and could be a contributing mechanism to progressive multiple sclerosis.
{"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":"10.1038/s41593-025-02113-y","url":null,"abstract":"Oxidized phosphatidylcholines (OxPCs) are neurotoxic byproducts of oxidative stress elevated in the central nervous system (CNS) during progressive multiple sclerosis (P-MS). How OxPCs contribute to the pathophysiology of P-MS is unclear. Here we show that stereotactic OxPC deposition in the CNS of mice induces a chronic compartmentalized lesion with pathological features similar to chronic active lesions found in P-MS. Using this model, we found that although microglia protected the CNS from chronic neurodegeneration, they were also replaced by monocyte-derived macrophages in chronic OxPC lesions. Aging, a risk factor for P-MS, altered microglial composition and exacerbated neurodegeneration in chronic OxPC lesions. Amelioration of disease pathology in Casp1/Casp4-deficient mice and by blockade of IL-1R1 indicate that IL-1β signaling contributes to chronic OxPC accumulation and neurodegeneration. These results highlight OxPCs and IL-1β as potential drivers of chronic neurodegeneration in MS and suggest that their neutralization could be effective for treating P-MS. In this study, Yu et al. found that a positive feedback loop between oxidized phosphatidylcholine and IL-1β promotes chronic neurodegeneration in the central nervous system and could be a contributing mechanism to progressive multiple sclerosis.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"29 1","pages":"67-80"},"PeriodicalIF":20.0,"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
Classical views of sensory perception describe a hierarchical organization, extending from the sensory periphery to static representations in the primary sensory cortex, with downstream regions supporting decision-making and action. There is growing evidence that suggests a more flexible role of primary sensory cortex, with behaviorally relevant functions distributed across multiple levels of the early sensory pathway that can change in response to context. In this Perspective, we first examine primary sensory cortex beyond sensory representations through the lens of sufficiency to predict behavior. We then consider the necessity of primary sensory cortex in sensory-driven behaviors, explored through a range of inactivation and lesioning studies. Finally, we provide evidence that points to an adaptive and flexible role for primary sensory cortex, where function is shaped by experience and context. This adaptive nature demands a more holistic investigative approach that challenges sensory pathways with adaptive behaviors in response to changing environments, behavioral contexts and injury. We challenge the traditional views of sensory processing, showing that primary sensory cortex has an adaptive and flexible role that evolves with learning and context, reshaping our understanding of perception, behavior and brain function.
{"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":"10.1038/s41593-025-02124-9","url":null,"abstract":"Classical views of sensory perception describe a hierarchical organization, extending from the sensory periphery to static representations in the primary sensory cortex, with downstream regions supporting decision-making and action. There is growing evidence that suggests a more flexible role of primary sensory cortex, with behaviorally relevant functions distributed across multiple levels of the early sensory pathway that can change in response to context. In this Perspective, we first examine primary sensory cortex beyond sensory representations through the lens of sufficiency to predict behavior. We then consider the necessity of primary sensory cortex in sensory-driven behaviors, explored through a range of inactivation and lesioning studies. Finally, we provide evidence that points to an adaptive and flexible role for primary sensory cortex, where function is shaped by experience and context. This adaptive nature demands a more holistic investigative approach that challenges sensory pathways with adaptive behaviors in response to changing environments, behavioral contexts and injury. We challenge the traditional views of sensory processing, showing that primary sensory cortex has an adaptive and flexible role that evolves with learning and context, reshaping our understanding of perception, behavior and brain function.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"29 1","pages":"2-12"},"PeriodicalIF":20.0,"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
Adult gliomas are incurable primary brain cancers that infiltrate healthy brain and incorporate into neural networks. Gliomas can be classified as low grade or high grade based on histopathological and molecular features, which broadly predicts their aggressiveness. Here we performed patch-clamp electrophysiological recordings from pyramidal neurons and glioma cells from individuals with either low- or high-grade glioma. We find that the biophysical properties of human pyramidal neurons within glioma-infiltrated cortex differ according to tumor grade, with neurons from high-grade glioma being more excitable than those from low-grade glioma. Additionally, glioma cells within high-grade tumors have smaller, longer synaptic responses. Increased neuron–glioma network activity within human high-grade tumor tissue leads to increased glioma proliferation, suggesting that the hyperexcitability of pyramidal neurons in human high-grade glioma may drive tumor growth. Combined, our findings illustrate that high- and low-grade glioma differentially hijack neural networks. Neurons within high-grade human gliomas were more electronically active than those within low-grade ones, and glioma cells in high-grade glioma had smaller but longer-lasting synaptic responses. Heightened neuron–glioma activity was associated with faster proliferation.
{"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":"10.1038/s41593-025-02149-0","url":null,"abstract":"Adult gliomas are incurable primary brain cancers that infiltrate healthy brain and incorporate into neural networks. Gliomas can be classified as low grade or high grade based on histopathological and molecular features, which broadly predicts their aggressiveness. Here we performed patch-clamp electrophysiological recordings from pyramidal neurons and glioma cells from individuals with either low- or high-grade glioma. We find that the biophysical properties of human pyramidal neurons within glioma-infiltrated cortex differ according to tumor grade, with neurons from high-grade glioma being more excitable than those from low-grade glioma. Additionally, glioma cells within high-grade tumors have smaller, longer synaptic responses. Increased neuron–glioma network activity within human high-grade tumor tissue leads to increased glioma proliferation, suggesting that the hyperexcitability of pyramidal neurons in human high-grade glioma may drive tumor growth. Combined, our findings illustrate that high- and low-grade glioma differentially hijack neural networks. Neurons within high-grade human gliomas were more electronically active than those within low-grade ones, and glioma cells in high-grade glioma had smaller but longer-lasting synaptic responses. Heightened neuron–glioma activity was associated with faster proliferation.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"29 2","pages":"350-357"},"PeriodicalIF":20.0,"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":"10.1038/s41593-025-02182-z","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"29 1","pages":"246-246"},"PeriodicalIF":20.0,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41593-025-02182-z.pdf","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：