Nature neuroscience最新文献_第9页

Challenges of the inconsistent neurorights framework in Latin America 拉丁美洲不一致的神经权利框架的挑战

IF 2 1区医学

Nature neuroscience Pub Date : 2025-06-18 DOI: 10.1038/s41593-025-02001-5

Diego Borbón

引用次数: 0

Myelin–axon interface vulnerability in Alzheimer’s disease revealed by subcellular proteomics and imaging of human and mouse brain 亚细胞蛋白质组学和人和小鼠脑成像揭示阿尔茨海默病髓磷脂-轴突界面易感性

IF 2 1区医学

Nature neuroscience Pub Date : 2025-06-13 DOI: 10.1038/s41593-025-01973-8

Yifei Cai, Iguaracy Pinheiro-de-Sousa, Mykhaylo Slobodyanyuk, Fuyi Chen, Tram Huynh, Jean Kanyo, Peiyang Tang, Lukas A. Fuentes, Amber Braker, Rachel Welch, Anita Huttner, Lei Tong, Peng Yuan, TuKiet T. Lam, Evangelia Petsalaki, Jüri Reimand, Angus C. Nairn, Jaime Grutzendler

{"title":"Myelin–axon interface vulnerability in Alzheimer’s disease revealed by subcellular proteomics and imaging of human and mouse brain","authors":"Yifei Cai, Iguaracy Pinheiro-de-Sousa, Mykhaylo Slobodyanyuk, Fuyi Chen, Tram Huynh, Jean Kanyo, Peiyang Tang, Lukas A. Fuentes, Amber Braker, Rachel Welch, Anita Huttner, Lei Tong, Peng Yuan, TuKiet T. Lam, Evangelia Petsalaki, Jüri Reimand, Angus C. Nairn, Jaime Grutzendler","doi":"10.1038/s41593-025-01973-8","DOIUrl":"10.1038/s41593-025-01973-8","url":null,"abstract":"Myelin ensheathment is essential for rapid axonal conduction, metabolic support and neuronal plasticity. In Alzheimer’s disease (AD), disruptions in myelin and axonal structures occur, although the underlying mechanisms remain unclear. We implemented proximity labeling subcellular proteomics of the myelin–axon interface in postmortem human brains from AD donors and 15-month-old male and female 5XFAD mice. We uncovered multiple dysregulated signaling pathways and ligand–receptor interactions, including those linked to amyloid-β processing, axonal outgrowth and lipid metabolism. Expansion microscopy confirmed the subcellular localization of top proteomic hits and revealed amyloid-β aggregation within the internodal periaxonal space and paranodal/juxtaparanodal channels. Although overall myelin coverage is preserved, we found reduced paranode density, aberrant myelination and altered paranode positioning around amyloid-plaque-associated dystrophic axons. These findings suggest that the myelin–axon interface is a critical site of protein aggregation and disrupted neuro-glial signaling in AD. In Alzheimer’s disease (AD), disruptions in myelin and axonal structures occur, although the underlying mechanisms remain unclear. Here the authors show that, at the myelin–axon interface, axon–glial signaling, paranodal architecture and amyloid-β aggregation are altered in AD, implicating myelin–axon disruption in disease progression.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 7","pages":"1418-1435"},"PeriodicalIF":20.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278506","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

The brain works at more than 10 bits per second 大脑的工作速度超过每秒10比特

IF 2 1区医学

Nature neuroscience Pub Date : 2025-06-13 DOI: 10.1038/s41593-025-01997-0

Britton A. Sauerbrei, J. Andrew Pruszynski

引用次数: 0

Protective exercise responses in the dentate gyrus of Alzheimer’s disease mouse model revealed with single-nucleus RNA-sequencing 单核rna测序揭示阿尔茨海默病小鼠齿状回的保护性运动反应

IF 2 1区医学

Nature neuroscience Pub Date : 2025-06-12 DOI: 10.1038/s41593-025-01971-w

Joana F. da Rocha, Michelle L. Lance, Renhao Luo, Pius Schlachter, Luis Moreira, Mohamed Ariff Iqbal, Paula Kuhn, Robert S. Gardner, Sophia Valaris, Mohammad R. Islam, Gabriele M. Gassner, Sofia Mazuera, Kaela Healy, Sanjana Shastri, Nathaniel B. Hibbert, Kristen V. Moran-Figueroa, Erin B. Haley, Ryan D. Pfeiffer, Sema Aygar, Ksenia V. Kastanenka, Logan Brase, Oscar Harari, Bruno A. Benitez, Nathan R. Tucker, Christiane D. Wrann

{"title":"Protective exercise responses in the dentate gyrus of Alzheimer’s disease mouse model revealed with single-nucleus RNA-sequencing","authors":"Joana F. da Rocha, Michelle L. Lance, Renhao Luo, Pius Schlachter, Luis Moreira, Mohamed Ariff Iqbal, Paula Kuhn, Robert S. Gardner, Sophia Valaris, Mohammad R. Islam, Gabriele M. Gassner, Sofia Mazuera, Kaela Healy, Sanjana Shastri, Nathaniel B. Hibbert, Kristen V. Moran-Figueroa, Erin B. Haley, Ryan D. Pfeiffer, Sema Aygar, Ksenia V. Kastanenka, Logan Brase, Oscar Harari, Bruno A. Benitez, Nathan R. Tucker, Christiane D. Wrann","doi":"10.1038/s41593-025-01971-w","DOIUrl":"10.1038/s41593-025-01971-w","url":null,"abstract":"Exercise’s protective effects in Alzheimer’s disease (AD) are well recognized, but cell-specific contributions to this phenomenon remain unclear. Here we used single-nucleus RNA sequencing (snRNA-seq) to dissect the response to exercise (free-wheel running) in the neurogenic stem-cell niche of the hippocampal dentate gyrus in male APP/PS1 transgenic AD model mice. Transcriptomic responses to exercise were distinct between wild-type and AD mice, and most prominent in immature neurons. Exercise restored the transcriptional profiles of a proportion of AD-dysregulated genes in a cell type-specific manner. We identified a neurovascular-associated astrocyte subpopulation, the abundance of which was reduced in AD, whereas its gene expression signature was induced with exercise. Exercise also enhanced the gene expression profile of disease-associated microglia. Oligodendrocyte progenitor cells were the cell type with the highest proportion of dysregulated genes recovered by exercise. Last, we validated our key findings in a human AD snRNA-seq dataset. Together, these data present a comprehensive resource for understanding the molecular mediators of neuroprotection by exercise in AD. Dissecting the adaptive exercise response of the neurogenic stem-cell niche in the dentate gyrus by single-nucleus RNA sequencing reveals the molecular mediators that underlie exercise’s protective effects in Alzheimer’s disease.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 7","pages":"1546-1561"},"PeriodicalIF":20.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268647","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

A flexible hippocampal population code for experience relative to reward 一个灵活的海马体群体编码相对于奖励的经验

IF 2 1区医学

Nature neuroscience Pub Date : 2025-06-11 DOI: 10.1038/s41593-025-01985-4

Marielena Sosa, Mark H. Plitt, Lisa M. Giocomo

{"title":"A flexible hippocampal population code for experience relative to reward","authors":"Marielena Sosa, Mark H. Plitt, Lisa M. Giocomo","doi":"10.1038/s41593-025-01985-4","DOIUrl":"10.1038/s41593-025-01985-4","url":null,"abstract":"To reinforce rewarding behaviors, events leading up to and following rewards must be remembered. Hippocampal place cell activity spans spatial and non-spatial episodes, but whether hippocampal activity encodes entire sequences of events relative to reward is unknown. Here, to test this possibility, we performed two-photon imaging of hippocampal CA1 as mice navigated virtual environments with changing hidden reward locations. We found that when the reward moved, a subpopulation of neurons updated their firing fields to the same relative position with respect to reward, constructing behavioral timescale sequences spanning the entire task. Over learning, this reward-relative representation became more robust as additional neurons were recruited, and changes in reward-relative firing often preceded behavioral adaptations following reward relocation. Concurrently, the spatial environment code was maintained through a parallel, dynamic subpopulation rather than through dedicated cell classes. These findings reveal how hippocampal ensembles flexibly encode multiple aspects of experience while amplifying behaviorally relevant information. Sosa et al. find that hippocampal neural activity in mice encodes both environmental location and experience relative to rewards, spanning distances far from reward, through parallel and flexible population-level codes.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 7","pages":"1497-1509"},"PeriodicalIF":20.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41593-025-01985-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260594","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

Suppression of binge alcohol drinking by an inhibitory neuronal ensemble in the mouse medial orbitofrontal cortex 小鼠内侧眶额叶皮质抑制神经元集合对酗酒的抑制

IF 2 1区医学

Nature neuroscience Pub Date : 2025-06-10 DOI: 10.1038/s41593-025-01970-x

Pablo Gimenez-Gomez, Timmy Le, Max Zinter, Peter M’Angale, Violeta Duran-Laforet, Timothy G. Freels, Rebecca Pavchinskiy, Susanna Molas, Dorothy P. Schafer, Andrew R. Tapper, Travis Thomson, Gilles E. Martin

{"title":"Suppression of binge alcohol drinking by an inhibitory neuronal ensemble in the mouse medial orbitofrontal cortex","authors":"Pablo Gimenez-Gomez, Timmy Le, Max Zinter, Peter M’Angale, Violeta Duran-Laforet, Timothy G. Freels, Rebecca Pavchinskiy, Susanna Molas, Dorothy P. Schafer, Andrew R. Tapper, Travis Thomson, Gilles E. Martin","doi":"10.1038/s41593-025-01970-x","DOIUrl":"10.1038/s41593-025-01970-x","url":null,"abstract":"Alcohol consumption remains a significant global health challenge, directly and indirectly causing millions of deaths annually. Alcohol abuse causes dysregulated activity of the prefrontal cortex, yet effects on specific prefrontal circuits remain to be elucidated. Here, we identify a discrete GABAergic neuronal ensemble in the mouse medial orbitofrontal cortex (mOFC) that is selectively recruited in response to binge alcohol drinking and limits further drinking behavior. Optogenetic silencing of this population, or its ablation, results in uncontrolled binge alcohol consumption. This neuronal ensemble is specific to alcohol and is not recruited by other rewarding substances. Neurons in this ensemble project widely throughout the brain, but projections specifically to the mediodorsal thalamus regulate binge alcohol drinking. Together, these results identify a brain circuit in the mOFC that serves to protect against binge drinking by reducing alcohol intake, which may offer avenues for the development of mOFC neuronal ensemble-targeted interventions. This study demonstrates that high alcohol concentrations during binge drinking activate a small GABAergic neuronal ensemble in the medial orbitofrontal cortex, which subsequently reduces further alcohol consumption. This effect is mediated by the ensemble’s projections to the mediodorsal thalamus.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 8","pages":"1741-1752"},"PeriodicalIF":20.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252309","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

A route for cerebrospinal fluid flow through leptomeningeal arterial–venous overlaps enables macromolecule and fluid shunting 脑脊液通过小脑膜动-静脉重叠的途径可以实现大分子和液体分流

IF 2 1区医学

Nature neuroscience Pub Date : 2025-06-09 DOI: 10.1038/s41593-025-01977-4

Benjamin A. Plog, Kyungdeok Kim, Daan Verhaege, Min Woo Kim, Zachary Papadopoulos, Krikor Dikranian, Taitea Dykstra, Jay Cao, Richard J. Perrin, Katherine E. Schwetye, Jonathan Kipnis, Antoine Drieu

{"title":"A route for cerebrospinal fluid flow through leptomeningeal arterial–venous overlaps enables macromolecule and fluid shunting","authors":"Benjamin A. Plog, Kyungdeok Kim, Daan Verhaege, Min Woo Kim, Zachary Papadopoulos, Krikor Dikranian, Taitea Dykstra, Jay Cao, Richard J. Perrin, Katherine E. Schwetye, Jonathan Kipnis, Antoine Drieu","doi":"10.1038/s41593-025-01977-4","DOIUrl":"10.1038/s41593-025-01977-4","url":null,"abstract":"The flow of cerebrospinal fluid (CSF) is important for conveying brain-derived macromolecules for signaling and enabling them to be drained from the brain parenchyma. The glymphatic route is the best-characterized means of this CSF flow; however, it does not permit the movement of larger macromolecules. Here, we identify in mice an alternative route whereby intra-CSF-injected macromolecules can traverse from periarterial to perivenous spaces, with transfer occurring at sites of overlap between leptomeningeal perivascular (arteriovenous) spaces dispersed across the surface of the brain’s leptomeninges. We show that intra-CSF-injected fluorescent tracers can reach the perivenous space by passing through these arteriovenous perivascular overlaps. These spaces remain functional in a mouse model of amyloidosis and are essential for clearing excess CSF volume. These anatomical structures may support brain function by allowing the drainage of brain-derived macromolecules and the shunting of excess fluid and by aiding the immune surveillance of freshly generated CSF. The authors describe a mechanism for the clearance of macromolecules from cerebrospinal fluid in which macromolecules traverse from periarterial to perivenous spaces, at sites where intersecting leptomeningeal perivascular (arteriovenous) spaces overlap.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 7","pages":"1436-1445"},"PeriodicalIF":20.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237997","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

Spatial reasoning via recurrent neural dynamics in mouse retrosplenial cortex 小鼠脾后皮层循环神经动力学的空间推理

IF 2 1区医学

Nature neuroscience Pub Date : 2025-06-06 DOI: 10.1038/s41593-025-01944-z

Jakob Voigts, Ingmar Kanitscheider, Nicholas J. Miller, Enrique H. S. Toloza, Jonathan P. Newman, Ila R. Fiete, Mark T. Harnett

{"title":"Spatial reasoning via recurrent neural dynamics in mouse retrosplenial cortex","authors":"Jakob Voigts, Ingmar Kanitscheider, Nicholas J. Miller, Enrique H. S. Toloza, Jonathan P. Newman, Ila R. Fiete, Mark T. Harnett","doi":"10.1038/s41593-025-01944-z","DOIUrl":"10.1038/s41593-025-01944-z","url":null,"abstract":"From visual perception to language, sensory stimuli change their meaning depending on previous experience. Recurrent neural dynamics can interpret stimuli based on externally cued context, but it is unknown whether they can compute and employ internal hypotheses to resolve ambiguities. Here we show that mouse retrosplenial cortex (RSC) can form several hypotheses over time and perform spatial reasoning through recurrent dynamics. In our task, mice navigated using ambiguous landmarks that are identified through their mutual spatial relationship, requiring sequential refinement of hypotheses. Neurons in RSC and in artificial neural networks encoded mixtures of hypotheses, location and sensory information, and were constrained by robust low-dimensional dynamics. RSC encoded hypotheses as locations in activity space with divergent trajectories for identical sensory inputs, enabling their correct interpretation. Our results indicate that interactions between internal hypotheses and external sensory data in recurrent circuits can provide a substrate for complex sequential cognitive reasoning. Using a spatial reasoning task in mice, the authors show that retrosplenial cortex encodes spatial hypotheses with well-behaved recurrent dynamics, which can combine these hypotheses with incoming information to resolve ambiguities.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 6","pages":"1293-1299"},"PeriodicalIF":20.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41593-025-01944-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228854","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

Tuning arousal 调优兴奋

IF 2 1区医学

Nature neuroscience Pub Date : 2025-06-06 DOI: 10.1038/s41593-025-01994-3

Laura Zelenka

引用次数: 0

Sleep cycles process memories 睡眠周期处理记忆

IF 2 1区医学

Nature neuroscience Pub Date : 2025-06-06 DOI: 10.1038/s41593-025-01996-1

William P. Olson

引用次数: 0