Nature neuroscience最新文献_第9页

Glioblastoma–neuron networks Glioblastoma-neuron网络

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-01-08 DOI: 10.1038/s41593-024-01862-6

Shari Wiseman

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AI beats neuroscientists’ predictions 人工智能打败了神经科学家的预测

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-01-08 DOI: 10.1038/s41593-024-01860-8

Henrietta Howells

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Multimodal transcriptomics reveal neurogenic aging trajectories and age-related regional inflammation in the dentate gyrus 多模态转录组学揭示了齿状回的神经源性衰老轨迹和与年龄相关的区域炎症

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-01-06 DOI: 10.1038/s41593-024-01848-4

Yicheng Wu, Vladyslav I. Korobeynyk, Margherita Zamboni, Felix Waern, John Darby Cole, Sarah Mundt, Melanie Greter, Jonas Frisén, Enric Llorens-Bobadilla, Sebastian Jessberger

{"title":"Multimodal transcriptomics reveal neurogenic aging trajectories and age-related regional inflammation in the dentate gyrus","authors":"Yicheng Wu, Vladyslav I. Korobeynyk, Margherita Zamboni, Felix Waern, John Darby Cole, Sarah Mundt, Melanie Greter, Jonas Frisén, Enric Llorens-Bobadilla, Sebastian Jessberger","doi":"10.1038/s41593-024-01848-4","DOIUrl":"10.1038/s41593-024-01848-4","url":null,"abstract":"The mammalian dentate gyrus (DG) is involved in certain forms of learning and memory, and DG dysfunction has been implicated in age-related diseases. Although neurogenic potential is maintained throughout life in the DG as neural stem cells (NSCs) continue to generate new neurons, neurogenesis decreases with advancing age, with implications for age-related cognitive decline and disease. In this study, we used single-cell RNA sequencing to characterize transcriptomic signatures of neurogenic cells and their surrounding DG niche, identifying molecular changes associated with neurogenic aging from the activation of quiescent NSCs to the maturation of fate-committed progeny. By integrating spatial transcriptomics data, we identified the regional invasion of inflammatory cells into the hippocampus with age and show here that early-onset neuroinflammation decreases neurogenic activity. Our data reveal the lifelong molecular dynamics of NSCs and their surrounding neurogenic DG niche with age and provide a powerful resource to understand age-related molecular alterations in the aging hippocampus. Multimodal transcriptomics unveil the molecular dynamics of neural stem cells and their surrounding niche in the aging mouse hippocampus and provide a resource to understand age-related molecular changes.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 2","pages":"415-430"},"PeriodicalIF":21.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01848-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929721","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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Context-dependent decision-making in the primate hippocampal–prefrontal circuit 灵长类动物海马体-前额叶回路中的情境依赖决策

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-01-06 DOI: 10.1038/s41593-024-01839-5

Thomas W. Elston, Joni D. Wallis

{"title":"Context-dependent decision-making in the primate hippocampal–prefrontal circuit","authors":"Thomas W. Elston, Joni D. Wallis","doi":"10.1038/s41593-024-01839-5","DOIUrl":"10.1038/s41593-024-01839-5","url":null,"abstract":"What is good in one scenario may be bad in another. Despite the ubiquity of such contextual reasoning in everyday choice, how the brain flexibly uses different valuation schemes across contexts remains unknown. We addressed this question by monitoring neural activity from the hippocampus (HPC) and orbitofrontal cortex (OFC) of two monkeys performing a state-dependent choice task. We found that HPC neurons encoded state information as it became available and then, at the time of choice, relayed this information to the OFC via theta synchronization. During choice, the OFC represented value in a state-dependent manner; many OFC neurons uniquely coded for value in only one state but not the other. This suggests a functional dissociation whereby the HPC encodes contextual information that is broadcast to the OFC via theta synchronization to select a state-appropriate value subcircuit, thereby allowing for contextual reasoning in value-based choice. The brain uses different valuation schemes across contexts. Elston and Wallis show this is supported by hippocampal encoding of context that is broadcast to prefrontal value subcircuits via theta synchronization.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 2","pages":"374-382"},"PeriodicalIF":21.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01839-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929723","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}

引用次数: 0

Aberrant splicing in Huntington’s disease accompanies disrupted TDP-43 activity and altered m6A RNA modification 亨廷顿病的异常剪接伴随着TDP-43活性的破坏和m6A RNA修饰的改变

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-01-06 DOI: 10.1038/s41593-024-01850-w

Thai B. Nguyen, Ricardo Miramontes, Carlos Chillon-Marinas, Roy Maimon, Sonia Vazquez-Sanchez, Alice L. Lau, Nicolette R. McClure, Zhuoxing Wu, Keona Q. Wang, Whitney E. England, Monika Singha, Jennifer T. Stocksdale, Marie Heath, Ki-Hong Jang, Sunhee Jung, Karen Ling, Paymann Jafar-nejad, Jharrayne I. McKnight, Leanne N. Ho, Osama Al Dalahmah, Richard L. M. Faull, Joan S. Steffan, Jack C. Reidling, Cholsoon Jang, Gina Lee, Don W. Cleveland, Clotilde Lagier-Tourenne, Robert C. Spitale, Leslie M. Thompson

{"title":"Aberrant splicing in Huntington’s disease accompanies disrupted TDP-43 activity and altered m6A RNA modification","authors":"Thai B. Nguyen, Ricardo Miramontes, Carlos Chillon-Marinas, Roy Maimon, Sonia Vazquez-Sanchez, Alice L. Lau, Nicolette R. McClure, Zhuoxing Wu, Keona Q. Wang, Whitney E. England, Monika Singha, Jennifer T. Stocksdale, Marie Heath, Ki-Hong Jang, Sunhee Jung, Karen Ling, Paymann Jafar-nejad, Jharrayne I. McKnight, Leanne N. Ho, Osama Al Dalahmah, Richard L. M. Faull, Joan S. Steffan, Jack C. Reidling, Cholsoon Jang, Gina Lee, Don W. Cleveland, Clotilde Lagier-Tourenne, Robert C. Spitale, Leslie M. Thompson","doi":"10.1038/s41593-024-01850-w","DOIUrl":"10.1038/s41593-024-01850-w","url":null,"abstract":"Huntington’s disease (HD) is caused by a CAG repeat expansion in the HTT gene, leading to altered gene expression. However, the mechanisms leading to disrupted RNA processing in HD remain unclear. Here we identify TDP-43 and the N6-methyladenosine (m6A) writer protein METTL3 to be upstream regulators of exon skipping in multiple HD systems. Disrupted nuclear localization of TDP-43 and cytoplasmic accumulation of phosphorylated TDP-43 occurs in HD mouse and human brains, with TDP-43 also co-localizing with HTT nuclear aggregate-like bodies distinct from mutant HTT inclusions. The binding of TDP-43 onto RNAs encoding HD-associated differentially expressed and aberrantly spliced genes is decreased. Finally, m6A RNA modification is reduced on RNAs abnormally expressed in the striatum of HD R6/2 mouse brain, including at clustered sites adjacent to TDP-43 binding sites. Our evidence supports TDP-43 loss of function coupled with altered m6A modification as a mechanism underlying alternative splicing in HD. Nguyen et al. identify TDP-43 and METTL3 as key regulators of disrupted RNA splicing in Huntington’s disease, offering insight into how TDP-43 mislocalization and aberrant m6A RNA modification and localization relate to disease pathogenesis.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 2","pages":"280-292"},"PeriodicalIF":21.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01850-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929446","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}

引用次数: 0

Typical development of synaptic and neuronal properties can proceed without microglia in the cortex and thalamus 典型的突触和神经元特性的发育可以在皮层和丘脑中没有小胶质细胞的情况下进行

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-01-06 DOI: 10.1038/s41593-024-01833-x

Mary O’Keeffe, Sam A. Booker, Darren Walsh, Mosi Li, Chloe Henley, Laura Simões de Oliveira, Mingshan Liu, Xingran Wang, Maria Banqueri, Katherine Ridley, Kosala N. Dissanayake, Cristina Martinez-Gonzalez, Kirsty J. Craigie, Deepali Vasoya, Tom Leah, Xin He, David A. Hume, Ian Duguid, Matthew F. Nolan, Jing Qiu, David J. A. Wyllie, Owen R. Dando, Alfredo Gonzalez-Sulser, Jian Gan, Clare Pridans, Peter C. Kind, Giles E. Hardingham

{"title":"Typical development of synaptic and neuronal properties can proceed without microglia in the cortex and thalamus","authors":"Mary O’Keeffe, Sam A. Booker, Darren Walsh, Mosi Li, Chloe Henley, Laura Simões de Oliveira, Mingshan Liu, Xingran Wang, Maria Banqueri, Katherine Ridley, Kosala N. Dissanayake, Cristina Martinez-Gonzalez, Kirsty J. Craigie, Deepali Vasoya, Tom Leah, Xin He, David A. Hume, Ian Duguid, Matthew F. Nolan, Jing Qiu, David J. A. Wyllie, Owen R. Dando, Alfredo Gonzalez-Sulser, Jian Gan, Clare Pridans, Peter C. Kind, Giles E. Hardingham","doi":"10.1038/s41593-024-01833-x","DOIUrl":"10.1038/s41593-024-01833-x","url":null,"abstract":"Brain-resident macrophages, microglia, have been proposed to have an active role in synaptic refinement and maturation, influencing plasticity and circuit-level connectivity. Here we show that several neurodevelopmental processes previously attributed to microglia can proceed without them. Using a genetically modified mouse that lacks microglia (Csf1r∆FIRE/∆FIRE), we find that intrinsic properties, synapse number and synaptic maturation are largely normal in the hippocampal CA1 region and somatosensory cortex at stages where microglia have been implicated. Seizure susceptibility and hippocampal-prefrontal cortex coherence in awake behaving animals, processes that are disrupted in mice deficient in microglia-enriched genes, are also normal. Similarly, eye-specific segregation of inputs into the lateral geniculate nucleus proceeds normally in the absence of microglia. Single-cell and single-nucleus transcriptomic analyses of neurons and astrocytes did not uncover any substantial perturbation caused by microglial absence. Thus, the brain possesses remarkable adaptability to execute developmental synaptic refinement, maturation and connectivity in the absence of microglia. Microglia are proposed to have a role in brain development through synaptic engulfment and paracrine signaling. O’Keeffe et al. show that certain neurodevelopmental processes attributed to microglia can proceed normally even in the absence of these cells.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 2","pages":"268-279"},"PeriodicalIF":21.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01833-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929726","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}

引用次数: 0

Monocyte-derived macrophages act as reinforcements when microglia fall short in Alzheimer’s disease 在阿尔茨海默病中，当小胶质细胞不足时，单核细胞来源的巨噬细胞起到增强作用

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-01-06 DOI: 10.1038/s41593-024-01847-5

Miguel A. Abellanas, Maitreyee Purnapatre, Chiara Burgaletto, Michal Schwartz

{"title":"Monocyte-derived macrophages act as reinforcements when microglia fall short in Alzheimer’s disease","authors":"Miguel A. Abellanas, Maitreyee Purnapatre, Chiara Burgaletto, Michal Schwartz","doi":"10.1038/s41593-024-01847-5","DOIUrl":"10.1038/s41593-024-01847-5","url":null,"abstract":"The central nervous system (CNS) is endowed with its own resident innate immune cells, the microglia. They constitute approximately 10% of the total cells within the CNS parenchyma and act as ‘sentinels’, sensing and mitigating any deviation from homeostasis. Nevertheless, under severe acute or chronic neurological injury or disease, microglia are unable to contain the damage, and the reparative activity of monocyte-derived macrophages (MDMs) is required. The failure of the microglia under such conditions could be an outcome of their prolonged exposure to hostile stimuli, leading to their exhaustion or senescence. Here, we describe the conditions under which the microglia fall short, focusing mainly on the context of Alzheimer’s disease, and shed light on the functions performed by MDMs. We discuss whether and how MDMs engage in cross-talk with the microglia, why their recruitment is often inadequate, and potential ways to augment their homing to the brain in a well-controlled manner. This article discusses a puzzling issue in brain pathology: why brain-resident microglia are insufficient for protection, and why myeloid cells are needed from the periphery. Several strategies are proposed to enhance their recruitment to the brain.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 3","pages":"436-445"},"PeriodicalIF":21.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929724","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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NOMPC ion channel hinge forms a gating spring that initiates mechanosensation NOMPC离子通道铰链形成一个闸门弹簧，启动机械感觉

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-01-06 DOI: 10.1038/s41593-024-01849-3

Philip Hehlert, Thomas Effertz, Ruo-Xu Gu, Björn Nadrowski, Bart R. H. Geurten, Dirk Beutner, Bert L. de Groot, Martin C. Göpfert

{"title":"NOMPC ion channel hinge forms a gating spring that initiates mechanosensation","authors":"Philip Hehlert, Thomas Effertz, Ruo-Xu Gu, Björn Nadrowski, Bart R. H. Geurten, Dirk Beutner, Bert L. de Groot, Martin C. Göpfert","doi":"10.1038/s41593-024-01849-3","DOIUrl":"10.1038/s41593-024-01849-3","url":null,"abstract":"The sensation of mechanical stimuli is initiated by elastic gating springs that pull open mechanosensory transduction channels. Searches for gating springs have focused on force-conveying protein tethers such as the amino-terminal ankyrin tether of the Drosophila mechanosensory transduction channel NOMPC. Here, by combining protein domain duplications with mechanical measurements, electrophysiology, molecular dynamics simulations and modeling, we identify the NOMPC gating-spring as the short linker between the ankyrin tether and the channel gate. This linker acts as a Hookean hinge that is ten times more elastic than the tether, with the linker hinge dictating channel gating and the intrinsic stiffness of the gating spring. Our study shows how mechanosensation is initiated molecularly; disentangles gating springs and tethers, and respective paradigms of channel gating; and puts forward gating springs as core ion channel constituents that enable efficient gating by diverse stimuli and in a wide variety of channels. Hehlert et al. report that the gating spring that pulls open mechanosensitive NOMPC channels is not their helical ankyrin tether, but instead an elastic hinge that suspends that tether on the channel gate.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 2","pages":"259-267"},"PeriodicalIF":21.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929722","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}

引用次数: 0

Cerebellar Bergmann glia integrate noxious information and modulate nocifensive behaviors 小脑伯格曼神经胶质整合有害信息并调节有害行为

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-01-02 DOI: 10.1038/s41593-024-01807-z

Seung Ha Kim, Jaegeon Lee, Mirae Jang, Seung-Eon Roh, Soobin Kim, Ji Hwan Lee, Jewoo Seo, Jinhee Baek, Jae Yoon Hwang, In Seon Baek, Yong-Seok Lee, Eiji Shigetomi, C. Justin Lee, Schuichi Koizumi, Sun Kwang Kim, Sang Jeong Kim

{"title":"Cerebellar Bergmann glia integrate noxious information and modulate nocifensive behaviors","authors":"Seung Ha Kim, Jaegeon Lee, Mirae Jang, Seung-Eon Roh, Soobin Kim, Ji Hwan Lee, Jewoo Seo, Jinhee Baek, Jae Yoon Hwang, In Seon Baek, Yong-Seok Lee, Eiji Shigetomi, C. Justin Lee, Schuichi Koizumi, Sun Kwang Kim, Sang Jeong Kim","doi":"10.1038/s41593-024-01807-z","DOIUrl":"10.1038/s41593-024-01807-z","url":null,"abstract":"The cerebellum is activated by noxious stimuli and pathological pain but its role in noxious information processing remains unknown. Here, we show that in mice, cutaneous noxious electrical stimuli induced noradrenaline (NA) release from locus coeruleus (LC) terminals in the cerebellar cortex. Bergmann glia (BG) accumulated these LC–NA signals by increasing intracellular calcium in an integrative manner (‘flares’). BG flares were also elicited in response to an intraplantar capsaicin injection. Chemogenetic inactivation of LC terminals or BG in the cerebellar cortex or BG-specific knockdown of α1-adrenergic receptors suppressed BG flares, reduced nocifensive licking and had analgesic effects in nerve injury-induced chronic neuropathic pain. Moreover, chemogenetic activation of BG or an intraplantar capsaicin injection reduced Purkinje cell firing, which may disinhibit the output activity of the deep cerebellar nuclei. These results suggest a role for BG in computing noxious information from the LC and in modulating pain-related behaviors by regulating cerebellar output. This study shows that cerebellar Bergmann glia process noxious stimuli by integrating signals from the locus coeruleus. This mechanism modulates pain-related behaviors. These findings provide insight into cerebellar involvement in pain processing.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 2","pages":"336-345"},"PeriodicalIF":21.2,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911423","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}

引用次数: 0

Negative self-experiences shape responses to others’ emotional states 消极的自我体验会影响对他人情绪状态的反应

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-01-02 DOI: 10.1038/s41593-024-01817-x

引用次数: 0