Nature neuroscience最新文献_第7页

The cell-type underpinnings of the human functional cortical connectome 人类大脑皮层功能连接体的细胞类型基础

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-11-21 DOI: 10.1038/s41593-024-01812-2

Xi-Han Zhang (, ), Kevin M. Anderson, Hao-Ming Dong (, ), Sidhant Chopra, Elvisha Dhamala, Prashant S. Emani, Mark B. Gerstein, Daniel S. Margulies, Avram J. Holmes

{"title":"The cell-type underpinnings of the human functional cortical connectome","authors":"Xi-Han Zhang \u0000 (, ), Kevin M. Anderson, Hao-Ming Dong \u0000 (, ), Sidhant Chopra, Elvisha Dhamala, Prashant S. Emani, Mark B. Gerstein, Daniel S. Margulies, Avram J. Holmes","doi":"10.1038/s41593-024-01812-2","DOIUrl":"10.1038/s41593-024-01812-2","url":null,"abstract":"The functional properties of the human brain arise, in part, from the vast assortment of cell types that pattern the cerebral cortex. The cortical sheet can be broadly divided into distinct networks, which are embedded into processing streams, or gradients, that extend from unimodal systems through higher-order association territories. Here using microarray data from the Allen Human Brain Atlas and single-nucleus RNA-sequencing data from multiple cortical territories, we demonstrate that cell-type distributions are spatially coupled to the functional organization of cortex, as estimated through functional magnetic resonance imaging. Differentially enriched cells follow the spatial topography of both functional gradients and associated large-scale networks. Distinct cellular fingerprints were evident across networks, and a classifier trained on postmortem cell-type distributions was able to predict the functional network allegiance of cortical tissue samples. These data indicate that the in vivo organization of the cortical sheet is reflected in the spatial variability of its cellular composition. Here Zhang et al. establish multiscale relationships that link postmortem cell-type distributions with the in vivo functional organization of the human cerebral cortex, as assessed through functional magnetic resonance imaging.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 1","pages":"150-160"},"PeriodicalIF":21.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678282","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 top-down slow breathing circuit that alleviates negative affect in mice 缓解小鼠负面情绪的自上而下缓慢呼吸回路

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-11-19 DOI: 10.1038/s41593-024-01799-w

Jinho Jhang, Seahyung Park, Shijia Liu, David D. O’Keefe, Sung Han

{"title":"A top-down slow breathing circuit that alleviates negative affect in mice","authors":"Jinho Jhang, Seahyung Park, Shijia Liu, David D. O’Keefe, Sung Han","doi":"10.1038/s41593-024-01799-w","DOIUrl":"10.1038/s41593-024-01799-w","url":null,"abstract":"Although breathing is primarily automatic, its modulation by behavior and emotions suggests cortical inputs to brainstem respiratory networks, which hitherto have received little characterization. Here we identify in mice a top-down breathing pathway from dorsal anterior cingulate cortex (dACC) neurons to pontine reticular nucleus GABAergic inhibitory neurons (PnCGABA), which then project to the ventrolateral medulla (VLM). dACC→PnC activity correlates with slow breathing cycles and volitional orofacial behaviors and is influenced by anxiogenic conditions. Optogenetic stimulation of the dACC→PnCGABA→VLM circuit simultaneously slows breathing and suppresses anxiety-like behaviors, whereas optogenetic inhibition increases both breathing rate and anxiety-like behaviors. These findings suggest that the dACC→PnCGABA→VLM circuit has a crucial role in coordinating slow breathing and reducing negative affect. Our study elucidates a circuit basis for top-down control of breathing, which can influence emotional states. Jhang et al. identify a prefrontal–pontomedullary pathway that slows breathing and reduces anxiety in mice, where the pontine reticular nucleus converts excitatory prefrontal inputs into inhibitory signals to brainstem respiratory networks.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2455-2465"},"PeriodicalIF":21.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142670687","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 revised view of the role of CaMKII in learning and memory 关于 CaMKII 在学习和记忆中的作用的新观点

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-11-18 DOI: 10.1038/s41593-024-01809-x

Karl Ulrich Bayer, Karl Peter Giese

引用次数: 0

Multimodal evaluation of network activity and optogenetic interventions in human hippocampal slices 对人类海马切片的网络活动和光遗传干预进行多模式评估

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-11-15 DOI: 10.1038/s41593-024-01782-5

John P. Andrews, Jinghui Geng, Kateryna Voitiuk, Matthew A. T. Elliott, David Shin, Ash Robbins, Alex Spaeth, Albert Wang, Lin Li, Daniel Solis, Matthew G. Keefe, Jessica L. Sevetson, Julio A. Rivera de Jesús, Kevin C. Donohue, H. Hanh Larson, Drew Ehrlich, Kurtis I. Auguste, Sofie Salama, Vikaas Sohal, Tal Sharf, David Haussler, Cathryn R. Cadwell, David V. Schaffer, Edward F. Chang, Mircea Teodorescu, Tomasz Jan Nowakowski

{"title":"Multimodal evaluation of network activity and optogenetic interventions in human hippocampal slices","authors":"John P. Andrews, Jinghui Geng, Kateryna Voitiuk, Matthew A. T. Elliott, David Shin, Ash Robbins, Alex Spaeth, Albert Wang, Lin Li, Daniel Solis, Matthew G. Keefe, Jessica L. Sevetson, Julio A. Rivera de Jesús, Kevin C. Donohue, H. Hanh Larson, Drew Ehrlich, Kurtis I. Auguste, Sofie Salama, Vikaas Sohal, Tal Sharf, David Haussler, Cathryn R. Cadwell, David V. Schaffer, Edward F. Chang, Mircea Teodorescu, Tomasz Jan Nowakowski","doi":"10.1038/s41593-024-01782-5","DOIUrl":"10.1038/s41593-024-01782-5","url":null,"abstract":"Seizures are made up of the coordinated activity of networks of neurons, suggesting that control of neurons in the pathologic circuits of epilepsy could allow for control of the disease. Optogenetics has been effective at stopping seizure-like activity in non-human disease models by increasing inhibitory tone or decreasing excitation, although this effect has not been shown in human brain tissue. Many of the genetic means for achieving channelrhodopsin expression in non-human models are not possible in humans, and vector-mediated methods are susceptible to species-specific tropism that may affect translational potential. Here we demonstrate adeno-associated virus–mediated, optogenetic reductions in network firing rates of human hippocampal slices recorded on high-density microelectrode arrays under several hyperactivity-provoking conditions. This platform can serve to bridge the gap between human and animal studies by exploring genetic interventions on network activity in human brain tissue. Brain slices offer an experimental window into human neurophysiology. Using high-density microelectrode array recordings and adeno-associated virus–mediated optogenetics, the authors demonstrate that optogenetic targeting of CAMK2A+ neurons can affect network activity in human hippocampal slices.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2487-2499"},"PeriodicalIF":21.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637068","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

Emergence of a brainstem somatosensory tonotopic map for substrate vibration 针对底物振动的脑干体感色调图谱的出现

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-11-15 DOI: 10.1038/s41593-024-01821-1

Kuo-Sheng Lee, Alastair J. Loutit, Dominica de Thomas Wagner, Mark Sanders, Daniel Huber

{"title":"Emergence of a brainstem somatosensory tonotopic map for substrate vibration","authors":"Kuo-Sheng Lee, Alastair J. Loutit, Dominica de Thomas Wagner, Mark Sanders, Daniel Huber","doi":"10.1038/s41593-024-01821-1","DOIUrl":"10.1038/s41593-024-01821-1","url":null,"abstract":"Perceiving substrate-borne vibrations is a fundamental component of tactile perception. How location (somatotopy) and frequency tuning (tonotopy) of vibrations are integratively processed is poorly understood. Here we addressed this question using in vivo electrophysiology and two-photon calcium imaging along the dorsal column–medial lemniscal pathway. We found that both frequency and location are organized into structured maps in the dorsal column nuclei (DCN). Both maps are intimately related at the fine spatial scale, with parallel map gradients that are consistent across the depth of the DCN and preserved along the ascending pathway. The tonotopic map only partially reflects the distribution of end organs in the skin and deep tissue; instead, the emergence of the fine-scale tonotopy is due to the selective dendritic sampling from axonal afferents, already at the first synaptic relay. We conclude that DCN neural circuits are key to the emergence of these two fine-scale topographical organizations in early somatosensory pathways. Lee et al. show that the development of the somatotopic map and the tonotopic map for substrate vibration is shaped by the intrinsic distribution of cutaneous end organs and selective dendritic integration within the brainstem dorsal column nuclei.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 1","pages":"97-104"},"PeriodicalIF":21.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637064","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

TYK2 regulates tau levels, phosphorylation and aggregation in a tauopathy mouse model TYK2 在牛磺酸病小鼠模型中调控牛磺酸水平、磷酸化和聚集

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-11-11 DOI: 10.1038/s41593-024-01777-2

Jiyoen Kim, Bakhos Tadros, Yan Hong Liang, Youngdoo Kim, Cristian Lasagna-Reeves, Jun Young Sonn, Dah-eun Chloe Chung, Bradley Hyman, David M. Holtzman, Huda Yahya Zoghbi

{"title":"TYK2 regulates tau levels, phosphorylation and aggregation in a tauopathy mouse model","authors":"Jiyoen Kim, Bakhos Tadros, Yan Hong Liang, Youngdoo Kim, Cristian Lasagna-Reeves, Jun Young Sonn, Dah-eun Chloe Chung, Bradley Hyman, David M. Holtzman, Huda Yahya Zoghbi","doi":"10.1038/s41593-024-01777-2","DOIUrl":"10.1038/s41593-024-01777-2","url":null,"abstract":"Alzheimer’s disease is one of at least 26 diseases characterized by tau-positive accumulation in neurons, glia or both. However, it is still unclear what modifications cause soluble tau to transform into insoluble aggregates. We previously performed genetic screens that identified tyrosine kinase 2 (TYK2) as a candidate regulator of tau levels. Here we verified this finding and found that TYK2 phosphorylates tau at tyrosine 29 (Tyr29) leading to its stabilization and promoting its aggregation in human cells. We discovered that TYK2-mediated Tyr29 phosphorylation interferes with autophagic clearance of tau. We also show that TYK2-mediated phosphorylation of Tyr29 facilitates pathological tau accumulation in P301S tau-transgenic mice. Furthermore, knockdown of Tyk2 reduced total tau and pathogenic tau levels and rescued gliosis in a tauopathy mouse model. Collectively, these data suggest that partial inhibition of TYK2 could thus be a strategy to reduce tau levels and toxicity. Tyrosine kinase 2 (TYK2) critically regulates tau levels and aggregation by phosphorylating tau’s tyrosine 29. Partial inhibition of TYK2 mitigates tau pathologies in cells and mice, highlighting TYK2 as a potential therapeutic target for Alzheimer’s disease and other tauopathies.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2417-2429"},"PeriodicalIF":21.2,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01777-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597969","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

Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease 星形胶质细胞转录组在阿尔茨海默病时空进展过程中的变化

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-11-11 DOI: 10.1038/s41593-024-01791-4

Alberto Serrano-Pozo, Huan Li, Zhaozhi Li, Clara Muñoz-Castro, Methasit Jaisa-aad, Molly A. Healey, Lindsay A. Welikovitch, Rojashree Jayakumar, Annie G. Bryant, Ayush Noori, Theresa R. Connors, Miwei Hu, Karen Zhao, Fan Liao, Gen Lin, Timothy Pastika, Joseph Tamm, Aicha Abdourahman, Taekyung Kwon, Rachel E. Bennett, Maya E. Woodbury, Astrid Wachter, Robert V. Talanian, Knut Biber, Eric H. Karran, Bradley T. Hyman, Sudeshna Das

{"title":"Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease","authors":"Alberto Serrano-Pozo, Huan Li, Zhaozhi Li, Clara Muñoz-Castro, Methasit Jaisa-aad, Molly A. Healey, Lindsay A. Welikovitch, Rojashree Jayakumar, Annie G. Bryant, Ayush Noori, Theresa R. Connors, Miwei Hu, Karen Zhao, Fan Liao, Gen Lin, Timothy Pastika, Joseph Tamm, Aicha Abdourahman, Taekyung Kwon, Rachel E. Bennett, Maya E. Woodbury, Astrid Wachter, Robert V. Talanian, Knut Biber, Eric H. Karran, Bradley T. Hyman, Sudeshna Das","doi":"10.1038/s41593-024-01791-4","DOIUrl":"10.1038/s41593-024-01791-4","url":null,"abstract":"Astrocytes are crucial to brain homeostasis, yet their changes along the spatiotemporal progression of Alzheimer’s disease (AD) neuropathology remain unexplored. Here we performed single-nucleus RNA sequencing of 628,943 astrocytes from five brain regions representing the stereotypical progression of AD pathology across 32 donors spanning the entire normal aging to severe AD continuum. We mapped out several unique astrocyte subclusters that exhibited varying responses to neuropathology across the AD-vulnerable neural network (spatial axis) or AD pathology stage (temporal axis). The proportion of homeostatic, intermediate and reactive astrocytes changed only along the spatial axis, whereas two other subclusters changed along the temporal axis. One of these, a trophic factor-rich subcluster, declined along pathology stages, whereas the other increased in the late stage but returned to baseline levels in the end stage, suggesting an exhausted response with chronic exposure to neuropathology. Our study underscores the complex dynamics of astrocytic responses in AD. Using single-nucleus RNA sequencing from 32 donors, researchers identified distinct astrocytic gene expression programs activated across brain regions and Alzheimer’s disease stages. They also found unique subclusters of astrocytes that appear to vary over time, highlighting the complexity of astrocytic responses in AD.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2384-2400"},"PeriodicalIF":21.2,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01791-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597925","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

Deep RNA sequencing of human dorsal root ganglion neurons reveals somatosensory mechanisms 人类背根神经节神经元的深度 RNA 测序揭示了躯体感觉机制

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-11-06 DOI: 10.1038/s41593-024-01795-0

引用次数: 0

Mapping out multiple sclerosis with spatial transcriptomics 利用空间转录组学绘制多发性硬化症地图

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-11-05 DOI: 10.1038/s41593-024-01798-x

Kellie Horan, Anna C. Williams

引用次数: 0

Spatially resolved gene signatures of white matter lesion progression in multiple sclerosis 多发性硬化症白质病变进展的空间分辨基因特征

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-11-05 DOI: 10.1038/s41593-024-01765-6

Astrid M. Alsema, Marion H. C. Wijering, Anneke Miedema, Janssen M. Kotah, Mirjam Koster, Merel Rijnsburger, Hilmar R. J. van Weering, Helga E. de Vries, Wia Baron, Susanne M. Kooistra, Bart J. L. Eggen

{"title":"Spatially resolved gene signatures of white matter lesion progression in multiple sclerosis","authors":"Astrid M. Alsema, Marion H. C. Wijering, Anneke Miedema, Janssen M. Kotah, Mirjam Koster, Merel Rijnsburger, Hilmar R. J. van Weering, Helga E. de Vries, Wia Baron, Susanne M. Kooistra, Bart J. L. Eggen","doi":"10.1038/s41593-024-01765-6","DOIUrl":"10.1038/s41593-024-01765-6","url":null,"abstract":"Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterized by myelin loss and progressive neurodegeneration. To understand MS lesion initiation and progression, we generate spatial gene expression maps of white matter (WM) and grey matter (GM) MS lesions. In different MS lesion types, we detect domains characterized by a distinct gene signature, including an identifiable rim around active WM lesions. Expression changes in astrocyte-specific, oligodendrocyte-specific and microglia-specific gene sets characterize the active lesion rims. Furthermore, we identify three WM lesion progression trajectories, predicting how normal-appearing WM can develop into WM active or mixed active–inactive lesions. Our data shed light on the dynamic progression of MS lesions. Lesion initiation and progression in multiple sclerosis is a dynamic but unclear process. Here, the authors highlight cell type-specific gene sets characterizing the action lesion rims and identify trajectories, predicting how normal-appearing white matter can develop into active and mixed active/inactive lesions.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2341-2353"},"PeriodicalIF":21.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580337","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