Nature neuroscience最新文献_第5页

A single-cell mass cytometry-based atlas of the developing mouse brain 发育中的小鼠大脑的单细胞细胞计数图谱

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-12-18 DOI: 10.1038/s41593-024-01786-1

Amy L. Van Deusen, Sushanth Kumar, O. Yipkin Calhan, Sarah M. Goggin, Jiachen Shi, Corey M. Williams, Austin B. Keeler, Kristen I. Fread, Irene C. Gadani, Christopher D. Deppmann, Eli R. Zunder

{"title":"A single-cell mass cytometry-based atlas of the developing mouse brain","authors":"Amy L. Van Deusen, Sushanth Kumar, O. Yipkin Calhan, Sarah M. Goggin, Jiachen Shi, Corey M. Williams, Austin B. Keeler, Kristen I. Fread, Irene C. Gadani, Christopher D. Deppmann, Eli R. Zunder","doi":"10.1038/s41593-024-01786-1","DOIUrl":"10.1038/s41593-024-01786-1","url":null,"abstract":"Development of the mammalian brain requires precise molecular changes across diverse cell lineages. While single-cell RNA abundances in the developing brain have been characterized by single-cell RNA sequencing (scRNA-seq), single-cell protein abundances have not been characterized. To address this gap, we performed mass cytometry on the whole brain at embryonic day (E)11.5–E12.5 and the telencephalon, the diencephalon, the mesencephalon and the rhombencephalon at E13.5–postnatal day (P)4 from C57/BL6 mice. Using a 40-antibody panel to analyze 24,290,787 cells from two to four biological replicates per sample, we identify 85 molecularly distinct cell clusters from distinct lineages. Our analyses confirm canonical molecular pathways of neurogenesis and gliogenesis, and predict two distinct trajectories for cortical oligodendrogenesis. Differences in protein versus RNA expression from mass cytometry and scRNA-seq, validated by immunohistochemistry and RNAscope in situ hybridization (ISH), demonstrate the value of protein-level measurements for identifying functional cell states. Our findings show the utility of mass cytometry as a scalable platform for single-cell profiling of brain tissues. In recent years, valuable mRNA-based developmental atlases of the mouse brain have been made available. Here, the authors use single-cell mass cytometry to build a protein-based single-cell profiling of the developing embryonic and postnatal mouse brain.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 1","pages":"174-188"},"PeriodicalIF":21.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841455","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

MeCP2 goes into unmethylated territories MeCP2 进入未甲基化区域

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-12-17 DOI: 10.1038/s41593-024-01846-6

Jun Young Sonn, Huda Y. Zoghbi

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Heat acclimation induces hypothalamic temperature sensitivity that promotes heat tolerance 热适应诱导下丘脑温度敏感性，促进耐热性

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-12-17 DOI: 10.1038/s41593-024-01835-9

引用次数: 0

Author Correction: Opportunities and challenges of single-cell and spatially resolved genomics methods for neuroscience discovery 作者更正：神经科学发现的单细胞和空间解决基因组学方法的机遇和挑战

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-12-16 DOI: 10.1038/s41593-024-01858-2

Boyan Bonev, Gonçalo Castelo-Branco, Fei Chen, Simone Codeluppi, M. Ryan Corces, Jean Fan, Myriam Heiman, Kenneth Harris, Fumitaka Inoue, Manolis Kellis, Ariel Levine, Mo Lotfollahi, Chongyuan Luo, Kristen R. Maynard, Mor Nitzan, Vijay Ramani, Rahul Satijia, Lucas Schirmer, Yin Shen, Na Sun, Gilad S. Green, Fabian Theis, Xiao Wang, Joshua D. Welch, Ozgun Gokce, Genevieve Konopka, Shane Liddelow, Evan Macosko, Omer Ali Bayraktar, Naomi Habib, Tomasz J. Nowakowski

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Simultaneous intracranial recordings of interacting brains reveal neurocognitive dynamics of human cooperation 对相互作用的大脑进行颅内同步记录，揭示人类合作的神经认知动力

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-12-13 DOI: 10.1038/s41593-024-01824-y

Jiaxin Wang, Fangang Meng, Cuiping Xu, Yanyang Zhang, Kun Liang, Chunlei Han, Yuan Gao, Xinguang Yu, Zizhou Li, Xiaoyu Zeng, Jun Ni, Huixin Tan, Jiaxin Yang, Yina Ma

{"title":"Simultaneous intracranial recordings of interacting brains reveal neurocognitive dynamics of human cooperation","authors":"Jiaxin Wang, Fangang Meng, Cuiping Xu, Yanyang Zhang, Kun Liang, Chunlei Han, Yuan Gao, Xinguang Yu, Zizhou Li, Xiaoyu Zeng, Jun Ni, Huixin Tan, Jiaxin Yang, Yina Ma","doi":"10.1038/s41593-024-01824-y","DOIUrl":"10.1038/s41593-024-01824-y","url":null,"abstract":"Cooperative interactions profoundly shape individual and collective behaviors of social animals. Successful cooperation requires coordinated efforts by cooperators toward collective goals. However, the underlying behavioral dynamics and neuronal mechanisms within and between cooperating brains remain largely unknown. We recorded intracranial electrophysiological signals from human pairs engaged in a cooperation game. We show that teammate coordination and goal pursuit make distinct contributions to the behavioral cooperation dynamics. Increases and decreases in high-gamma activity in the temporoparietal junction (TPJ) and amygdala distinguish between establishing and maintaining cooperation and forecast transitions between these two states. High-gamma activity from distinct neuronal populations encodes teammate coordination and goal pursuit motives, with populations of TPJ neurons preferentially tracking dominant motives of different cooperation states. Across cooperating brains, high-gamma activity in the TPJ and amygdala synchronizes in a state-dependent manner that predicts how well cooperators coordinate. These findings provide fine-grained understandings of human cooperation dynamics as a state-dependent process with distinctive neurocognitive profiles of each state. Using intracranial recordings in pairs of humans cooperating in interactive games, this study shows fine-grained cooperation dynamics featured by state-dependent motives and the intrabrain and interbrain profiles of high-gamma activity in the amygdala and temporoparietal junction.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 1","pages":"161-173"},"PeriodicalIF":21.2,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815722","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

Author Correction: Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain 作者更正：通过小鼠和人类大脑的单细胞测序来解剖人造的和混淆的神经胶质特征

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-12-13 DOI: 10.1038/s41593-024-01855-5

Samuel E. Marsh, Alec J. Walker, Tushar Kamath, Lasse Dissing-Olesen, Timothy R. Hammond, T. Yvanka de Soysa, Adam M. H. Young, Sarah Murphy, Abdulraouf Abdulraouf, Naeem Nadaf, Connor Dufort, Alicia C. Walker, Liliana E. Lucca, Velina Kozareva, Charles Vanderburg, Soyon Hong, Harry Bulstrode, Peter J. Hutchinson, Daniel J. Gaffney, David A. Hafler, Robin J. M. Franklin, Evan Z. Macosko, Beth Stevens

引用次数: 0

Amygdala intercalated cells form an evolutionarily conserved system orchestrating brain networks 杏仁核嵌入细胞形成了一个进化上保守的协调大脑网络的系统

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-12-13 DOI: 10.1038/s41593-024-01836-8

Ayla Aksoy-Aksel, Francesco Ferraguti, Andrew Holmes, Andreas Lüthi, Ingrid Ehrlich

{"title":"Amygdala intercalated cells form an evolutionarily conserved system orchestrating brain networks","authors":"Ayla Aksoy-Aksel, Francesco Ferraguti, Andrew Holmes, Andreas Lüthi, Ingrid Ehrlich","doi":"10.1038/s41593-024-01836-8","DOIUrl":"10.1038/s41593-024-01836-8","url":null,"abstract":"The amygdala attributes valence and emotional salience to environmental stimuli and regulates how these stimuli affect behavior. Within the amygdala, a distinct class of evolutionarily conserved neurons form the intercalated cell (ITC) clusters, mainly located around the boundaries of the lateral and basal nuclei. Here, we review the anatomical, physiological and molecular characteristics of ITCs, and detail the organization of ITC clusters and their connectivity with one another and other brain regions. We describe how ITCs undergo experience-dependent plasticity and discuss emerging evidence demonstrating how ITCs are innervated and functionally regulated by neuromodulatory systems. We summarize recent findings showing that experience alters the balance of activity between different ITC clusters, thereby determining prevailing behavioral output. Finally, we propose a model in which ITCs form a key system for integrating divergent inputs and orchestrating brain-wide circuits to generate behavioral states attuned to current environmental circumstances and internal needs. This comprehensive review of amygdala intercalated cells (ITCs) proposes a revised model of ITCs as a highly coordinated system that integrates diverse inputs to orchestrate brain-wide networks and shape behavioral states.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 2","pages":"234-247"},"PeriodicalIF":21.2,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815739","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

An RNA editing strategy rescues gene duplication in a mouse model of MECP2 duplication syndrome and nonhuman primates RNA编辑策略在MECP2复制综合征小鼠模型和非人灵长类动物中拯救基因复制

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-12-12 DOI: 10.1038/s41593-024-01838-6

Dong Yang, Xiaoqing Wu, Yinan Yao, Mengsi Duan, Xing Wang, Guoling Li, Aiguo Guo, Meixian Wu, Yuanhua Liu, Jin Zheng, Renxia Zhang, Tong Li, Alvin Luk, Xuan Yao, Linyu Shi, Chunlong Xu, Hui Yang

{"title":"An RNA editing strategy rescues gene duplication in a mouse model of MECP2 duplication syndrome and nonhuman primates","authors":"Dong Yang, Xiaoqing Wu, Yinan Yao, Mengsi Duan, Xing Wang, Guoling Li, Aiguo Guo, Meixian Wu, Yuanhua Liu, Jin Zheng, Renxia Zhang, Tong Li, Alvin Luk, Xuan Yao, Linyu Shi, Chunlong Xu, Hui Yang","doi":"10.1038/s41593-024-01838-6","DOIUrl":"10.1038/s41593-024-01838-6","url":null,"abstract":"Duplication of methyl-CpG-binding protein 2 (MECP2) gene causes MECP2 duplication syndrome (MDS). To normalize the duplicated MECP2 in MDS, we developed a high-fidelity Cas13Y (hfCas13Y) system capable of targeting the MECP2 (hfCas13Y-gMECP2) messenger RNA for degradation and reducing protein levels in the brain of humanized MECP2 transgenic mice. Moreover, the intracerebroventricular adeno-associated virus (AAV) delivery of hfCas13Y-gMECP2 in newborn or adult MDS mice restored dysregulated gene expression and improved behavior deficits. Notably, treatment with AAV9-hfCas13Y-gMECP2 extended the median survival of MECP2 transgenic mice from 156.5 to 226 d. Furthermore, studies with monkeys showed a single injection of AAV9-hfCas13Y-gMECP2 was sufficient to drive robust expression of hfCas13Y in widespread brain regions, with MECP2 knockdown efficiency reaching 52.19 ± 0.03% and significantly decreased expression of biomarker gene GDF11. Our results demonstrate that the RNA-targeting hfCas13Y-gMECP2 system is an effective intervention for MDS, providing a potential strategy for treating other dosage-sensitive diseases. Duplication of the MECP2 gene (encoding methyl-CpG-binding protein 2) causes MECP2 duplication syndrome. Here the authors develop a Cas13Y system capable of targeting the MECP2 mRNA for degradation and reducing protein levels in the brain of humanized MECP2-transgenic mice and nonhuman primates.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 1","pages":"72-83"},"PeriodicalIF":21.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809883","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

Microglia as hunters or gatherers of brain synapses 小胶质细胞是大脑突触的猎人或采集者

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-12-11 DOI: 10.1038/s41593-024-01818-w

Marta Pereira-Iglesias, Joel Maldonado-Teixido, Alejandro Melero, Joaquin Piriz, Elena Galea, Richard M. Ransohoff, Amanda Sierra

{"title":"Microglia as hunters or gatherers of brain synapses","authors":"Marta Pereira-Iglesias, Joel Maldonado-Teixido, Alejandro Melero, Joaquin Piriz, Elena Galea, Richard M. Ransohoff, Amanda Sierra","doi":"10.1038/s41593-024-01818-w","DOIUrl":"10.1038/s41593-024-01818-w","url":null,"abstract":"Over a decade ago, it was discovered that microglia, the brain’s immune cells, engulf synaptic material in a process named microglial pruning. This term suggests that microglia actively sculpt brain circuits by tagging and phagocytosing unwanted synapses. However, live imaging studies have yet to demonstrate how microglial synapse elimination occurs. To address this issue, we propose a new conceptual framework distinguishing between two potential mechanisms of synapse elimination, culling and scavenging. During culling, microglia may use a contractile ring to sever the neuronal plasma membrane, removing the unwanted synapse. During scavenging, synapse elimination is neuronal-driven, and the neuronal plasma membrane fission machinery sheds off synapses that are later phagocytosed by microglia. We will discuss the current limitations of studying microglial synapse elimination and evaluate evidence supporting either culling or scavenging. Discerning between these mechanisms is essential for determining the therapeutic value of phagocytosis modulators in diseases with altered brain connectivity. How microglia sculpt brain circuits is not clear. Here, the authors propose that their contribution to synapse removal may occur by severing synapses (culling) or collecting synapses shed off by neurons (scavenging).","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 1","pages":"15-23"},"PeriodicalIF":21.2,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804653","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

Stepwise molecular specification of excitatory synapse diversity onto cerebellar Purkinje cells 小脑浦肯野细胞兴奋性突触多样性的逐步分子表征

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-12-10 DOI: 10.1038/s41593-024-01826-w

Maëla A. Paul, Séverine M. Sigoillot, Léa Marti, Francisco J. Urra Quiroz, Marine Delagrange, Hiu W. Cheung, David C. Martinelli, Elie Oriol, Vincent Hakim, Philippe Mailly, Fekrije Selimi

{"title":"Stepwise molecular specification of excitatory synapse diversity onto cerebellar Purkinje cells","authors":"Maëla A. Paul, Séverine M. Sigoillot, Léa Marti, Francisco J. Urra Quiroz, Marine Delagrange, Hiu W. Cheung, David C. Martinelli, Elie Oriol, Vincent Hakim, Philippe Mailly, Fekrije Selimi","doi":"10.1038/s41593-024-01826-w","DOIUrl":"10.1038/s41593-024-01826-w","url":null,"abstract":"Brain function relies on the generation of a large variety of morphologically and functionally diverse, but specific, neuronal synapses. Here we show that, in mice, the initial formation of synapses on cerebellar Purkinje cells involves a presynaptic protein—CBLN1, a member of the C1q protein family—that is secreted by all types of excitatory inputs. The molecular program then evolves only in one of the Purkinje cell inputs, the inferior olivary neurons, with the additional expression of the presynaptic secreted proteins C1QL1, CRTAC1 and LGI2. These molecules work in concert to specify the mature connectivity pattern on the Purkinje cell target. These results show that some inputs actively and gradually specify their synaptic molecular identity, while others rely on the ‘original molecular code’. Thus, the molecular specification of excitatory synapses, crucial for proper circuit function, is acquired in a stepwise manner during mouse postnatal development and obeys input-specific rules. Brain function requires the formation of diverse and specific synapses. The authors show that the molecular code specifying excitatory connectivity on Purkinje cells evolves in an input-specific manner with postnatal circuit maturation.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 2","pages":"308-319"},"PeriodicalIF":21.2,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797144","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