Nature neuroscience最新文献_第6页

Membrane mechanics dictate axonal pearls-on-a-string morphology and function 膜力学决定轴突串珠的形态和功能

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-12-02 DOI: 10.1038/s41593-024-01813-1

Jacqueline M. Griswold, Mayte Bonilla-Quintana, Renee Pepper, Christopher T. Lee, Sumana Raychaudhuri, Siyi Ma, Quan Gan, Sarah Syed, Cuncheng Zhu, Miriam Bell, Mitsuo Suga, Yuuki Yamaguchi, Ronan Chéreau, U. Valentin Nägerl, Graham Knott, Padmini Rangamani, Shigeki Watanabe

{"title":"Membrane mechanics dictate axonal pearls-on-a-string morphology and function","authors":"Jacqueline M. Griswold, Mayte Bonilla-Quintana, Renee Pepper, Christopher T. Lee, Sumana Raychaudhuri, Siyi Ma, Quan Gan, Sarah Syed, Cuncheng Zhu, Miriam Bell, Mitsuo Suga, Yuuki Yamaguchi, Ronan Chéreau, U. Valentin Nägerl, Graham Knott, Padmini Rangamani, Shigeki Watanabe","doi":"10.1038/s41593-024-01813-1","DOIUrl":"10.1038/s41593-024-01813-1","url":null,"abstract":"Axons are ultrathin membrane cables that are specialized for the conduction of action potentials. Although their diameter is variable along their length, how their morphology is determined is unclear. Here, we demonstrate that unmyelinated axons of the mouse central nervous system have nonsynaptic, nanoscopic varicosities ~200 nm in diameter repeatedly along their length interspersed with a thin cable ~60 nm in diameter like pearls-on-a-string. In silico modeling suggests that this axon nanopearling can be explained by membrane mechanical properties. Treatments disrupting membrane properties, such as hyper- or hypotonic solutions, cholesterol removal and nonmuscle myosin II inhibition, alter axon nanopearling, confirming the role of membrane mechanics in determining axon morphology. Furthermore, neuronal activity modulates plasma membrane cholesterol concentration, leading to changes in axon nanopearls and causing slowing of action potential conduction velocity. These data reveal that biophysical forces dictate axon morphology and function, and modulation of membrane mechanics likely underlies unmyelinated axonal plasticity. Axons have always been assumed to be cylindrical. Using in silico modeling and cryopreservation of tissues, Griswold et al. demonstrate that unmyelinated axons of the mammalian central nervous system exhibit pearls-on-a-string morphology through their entire length.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 1","pages":"49-61"},"PeriodicalIF":21.2,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01813-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758195","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

Autism spectrum disorder variation as a computational trade-off via dynamic range of neuronal population responses 自闭症谱系障碍变异是通过神经元群体反应的动态范围进行计算权衡的结果

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-11-27 DOI: 10.1038/s41593-024-01800-6

Oded Wertheimer, Yuval Hart

{"title":"Autism spectrum disorder variation as a computational trade-off via dynamic range of neuronal population responses","authors":"Oded Wertheimer, Yuval Hart","doi":"10.1038/s41593-024-01800-6","DOIUrl":"10.1038/s41593-024-01800-6","url":null,"abstract":"Individuals diagnosed with autism spectrum disorder (ASD) show neural and behavioral characteristics differing from the neurotypical population. This may stem from a computational principle that relates inference and computational dynamics to the dynamic range of neuronal population responses, reflecting the signal levels for which the system is responsive. In the present study, we showed that an increased dynamic range (IDR), indicating a gradual response of a neuronal population to changes in input, accounts for neural and behavioral variations in individuals diagnosed with ASD across diverse tasks. We validated the model with data from finger-tapping synchronization, orientation reproduction and global motion coherence tasks. We suggested that increased heterogeneity in the half-activation point of individual neurons may be the biological mechanism underlying the IDR in ASD. Taken together, this model provides a proof of concept for a new computational principle that may account for ASD and generates new testable and distinct predictions regarding its behavioral, neural and biological foundations. Individuals with autism spectrum disorder show neural patterns different from those of neurotypical individuals. Here the authors show that this variation reflects a computational trade-off between accurate encoding and fast adaptation tuned by the neural population response.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2476-2486"},"PeriodicalIF":21.2,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01800-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718339","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

Wiring of a low-dimensional integrator network 低维积分器网络布线

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-11-26 DOI: 10.1038/s41593-024-01702-7

Bo Hu, Rainer W. Friedrich

引用次数: 0

Klaus A. Miczek (1945–2024) 克劳斯-米切克（1945-2024）

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-11-26 DOI: 10.1038/s41593-024-01837-7

Elise M. Weerts, Margaret Haney, Jennifer W. Tidey, Jeffrey A. Vivian

引用次数: 0

Infraslow noradrenergic locus coeruleus activity fluctuations are gatekeepers of the NREM–REM sleep cycle 下流去甲肾上腺素能区域小脑活动波动是 NREM-REM 睡眠周期的守门员

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-11-25 DOI: 10.1038/s41593-024-01822-0

Alejandro Osorio-Forero, Georgios Foustoukos, Romain Cardis, Najma Cherrad, Christiane Devenoges, Laura M. J. Fernandez, Anita Lüthi

{"title":"Infraslow noradrenergic locus coeruleus activity fluctuations are gatekeepers of the NREM–REM sleep cycle","authors":"Alejandro Osorio-Forero, Georgios Foustoukos, Romain Cardis, Najma Cherrad, Christiane Devenoges, Laura M. J. Fernandez, Anita Lüthi","doi":"10.1038/s41593-024-01822-0","DOIUrl":"10.1038/s41593-024-01822-0","url":null,"abstract":"The noradrenergic locus coeruleus (LC) regulates arousal levels during wakefulness, but its role in sleep remains unclear. Here, we show in mice that fluctuating LC neuronal activity partitions non-rapid-eye-movement sleep (NREMS) into two brain–autonomic states that govern the NREMS–REMS cycle over ~50-s periods; high LC activity induces a subcortical–autonomic arousal state that facilitates cortical microarousals, whereas low LC activity is required for NREMS-to-REMS transitions. This functional alternation regulates the duration of the NREMS–REMS cycle by setting permissive windows for REMS entries during undisturbed sleep while limiting these entries to maximally one per ~50-s period during REMS restriction. A stimulus-enriched, stress-promoting wakefulness was associated with longer and shorter levels of high and low LC activity, respectively, during subsequent NREMS, resulting in more microarousal-induced NREMS fragmentation and delayed REMS onset. We conclude that LC activity fluctuations are gatekeepers of the NREMS–REMS cycle and that this role is influenced by adverse wake experiences. Lüthi and colleagues show that activity of the locus coeruleus (LC) is crucial for the cyclic alternation between non-rapid-eye-movement and rapid-eye-movement sleep. Stressful experiences during waking can disrupt LC activity in sleep, which disorganizes the sleep cycle and increases microarousals.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 1","pages":"84-96"},"PeriodicalIF":21.2,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696562","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

Predicting modular functions and neural coding of behavior from a synaptic wiring diagram 从突触线路图预测行为的模块功能和神经编码

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-11-22 DOI: 10.1038/s41593-024-01784-3

Ashwin Vishwanathan, Alex Sood, Jingpeng Wu, Alexandro D. Ramirez, Runzhe Yang, Nico Kemnitz, Dodam Ih, Nicholas Turner, Kisuk Lee, Ignacio Tartavull, William M. Silversmith, Chris S. Jordan, Celia David, Doug Bland, Amy Sterling, H. Sebastian Seung, Mark S. Goldman, Emre R. F. Aksay, the Eyewirers

{"title":"Predicting modular functions and neural coding of behavior from a synaptic wiring diagram","authors":"Ashwin Vishwanathan, Alex Sood, Jingpeng Wu, Alexandro D. Ramirez, Runzhe Yang, Nico Kemnitz, Dodam Ih, Nicholas Turner, Kisuk Lee, Ignacio Tartavull, William M. Silversmith, Chris S. Jordan, Celia David, Doug Bland, Amy Sterling, H. Sebastian Seung, Mark S. Goldman, Emre R. F. Aksay, the Eyewirers","doi":"10.1038/s41593-024-01784-3","DOIUrl":"10.1038/s41593-024-01784-3","url":null,"abstract":"A long-standing goal in neuroscience is to understand how a circuit’s form influences its function. Here, we reconstruct and analyze a synaptic wiring diagram of the larval zebrafish brainstem to predict key functional properties and validate them through comparison with physiological data. We identify modules of strongly connected neurons that turn out to be specialized for different behavioral functions, the control of eye and body movements. The eye movement module is further organized into two three-block cycles that support the positive feedback long hypothesized to underlie low-dimensional attractor dynamics in oculomotor control. We construct a neural network model based directly on the reconstructed wiring diagram that makes predictions for the cellular-resolution coding of eye position and neural dynamics. These predictions are verified statistically with calcium imaging-based neural activity recordings. This work demonstrates how connectome-based brain modeling can reveal previously unknown anatomical structure in a neural circuit and provide insights linking network form to function. The authors determine the synaptic wiring diagram of a vertebrate circuit and reveal behaviorally associated modules. A model based on this connectome predicts neural coding and dynamics that are verified with calcium imaging data.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2443-2454"},"PeriodicalIF":21.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01784-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684165","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

Interaction of methyl-CpG-binding protein 2 (MeCP2) with distinct enhancers in the mouse cortex 甲基-CpG 结合蛋白 2（MeCP2）与小鼠皮层中不同增强子的相互作用

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-11-22 DOI: 10.1038/s41593-024-01808-y

Gyan Prakash Mishra, Eric X. Sun, Tiffany Chin, Mandy Eckhardt, Michael E. Greenberg, Hume Stroud

{"title":"Interaction of methyl-CpG-binding protein 2 (MeCP2) with distinct enhancers in the mouse cortex","authors":"Gyan Prakash Mishra, Eric X. Sun, Tiffany Chin, Mandy Eckhardt, Michael E. Greenberg, Hume Stroud","doi":"10.1038/s41593-024-01808-y","DOIUrl":"10.1038/s41593-024-01808-y","url":null,"abstract":"Mutations in methyl-CpG-binding protein 2 (MeCP2) cause Rett syndrome. MeCP2 is thought to regulate gene transcription by binding to methylated DNA broadly across the genome. Here, using cleavage under target and release under nuclease (CUT&RUN) assays in the adult mouse cortex, we show that MeCP2 strongly binds to specific gene enhancers that we call MeCP2-binding hotspots (MBHs). Unexpectedly, we find that MeCP2 binding to MBHs occurs in a DNA methylation-independent manner at MBHs. Multiple MBH sites surrounding genes mediate the transcriptional repression of genes enriched for neuronal functions. We show that MBHs regulate genes irrespective of genic methylation levels, suggesting that MeCP2 controls transcription via an intragenic methylation-independent mechanism. Hence, disruption of intragenic methylation-independent gene regulation by MeCP2 may in part underlie Rett syndrome. The Rett syndrome protein MeCP2 regulates gene transcription by binding to methylated DNA. Here the authors find that MeCP2 also regulates key neuronal genes by binding to nonmethylated DNA, providing new insights into the disorder.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 1","pages":"62-71"},"PeriodicalIF":21.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684166","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 initiative: a pioneering program on the precipice 脑神经网络计划：濒临绝境的开创性计划

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-11-22 DOI: 10.1038/s41593-024-01811-3

Cory T. Miller, Xiaoke Chen, Zoe R. Donaldson, Bianca Jones Marlin, Doris Y. Tsao, Ziv M. Williams, Moriel Zelikowsky, Hongkui Zeng, Weizhe Hong

引用次数: 0

Tau filaments are tethered within brain extracellular vesicles in Alzheimer’s disease 阿尔茨海默氏症患者脑细胞外囊泡内的 Tau 细丝被拴住了

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-11-21 DOI: 10.1038/s41593-024-01801-5

Stephanie L. Fowler, Tiana S. Behr, Emir Turkes, Darragh P. O’Brien, Paula Maglio Cauhy, Isadora Rawlinson, Marisa Edmonds, Martha S. Foiani, Ari Schaler, Gerard Crowley, Sumi Bez, Elena Ficulle, Eliona Tsefou, Roman Fischer, Beth Geary, Pallavi Gaur, Chelsea Miller, Pasquale D’Acunzo, Efrat Levy, Karen E. Duff, Benjamin Ryskeldi-Falcon

{"title":"Tau filaments are tethered within brain extracellular vesicles in Alzheimer’s disease","authors":"Stephanie L. Fowler, Tiana S. Behr, Emir Turkes, Darragh P. O’Brien, Paula Maglio Cauhy, Isadora Rawlinson, Marisa Edmonds, Martha S. Foiani, Ari Schaler, Gerard Crowley, Sumi Bez, Elena Ficulle, Eliona Tsefou, Roman Fischer, Beth Geary, Pallavi Gaur, Chelsea Miller, Pasquale D’Acunzo, Efrat Levy, Karen E. Duff, Benjamin Ryskeldi-Falcon","doi":"10.1038/s41593-024-01801-5","DOIUrl":"10.1038/s41593-024-01801-5","url":null,"abstract":"The abnormal assembly of tau protein in neurons is a pathological hallmark of multiple neurodegenerative diseases, including Alzheimer’s disease (AD). Assembled tau associates with extracellular vesicles (EVs) in the central nervous system of individuals with AD, which is linked to its clearance and prion-like propagation. However, the identities of the assembled tau species and EVs, as well as how they associate, are not known. Here, we combined quantitative mass spectrometry, cryo-electron tomography and single-particle cryo-electron microscopy to study brain EVs from individuals with AD. We found tau filaments composed mainly of truncated tau that were enclosed within EVs enriched in endo-lysosomal proteins. We observed multiple filament interactions, including with molecules that tethered filaments to the EV limiting membrane, suggesting selective packaging. Our findings will guide studies into the molecular mechanisms of EV-mediated secretion of assembled tau and inform the targeting of EV-associated tau as potential therapeutic and biomarker strategies for AD. Using cryo-electron tomography (cryo-ET) and proteomics, this study identifies the tethering of pathological tau filaments within defined brain extracellular vesicles in Alzheimer’s disease, shining light on the link between these vesicles and tau pathology.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 1","pages":"40-48"},"PeriodicalIF":21.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01801-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678283","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

Converging cortical axes 汇聚的皮层轴

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-11-21 DOI: 10.1038/s41593-024-01722-3

Konrad Wagstyl, Armin Raznahan

引用次数: 0