Nature neuroscience最新文献_第4页

Aging and injury drive neuronal senescence in the dorsal root ganglia 衰老和损伤驱动背根神经节神经元衰老

IF 25 1区医学

Nature neuroscience Pub Date : 2025-05-14 DOI: 10.1038/s41593-025-01954-x

Lauren J. Donovan, Chelsie L. Brewer, Sabrina F. Bond, Alexander M. Laslavic, Aleishai Pena Lopez, Laura Colman, Claire E. Jordan, Linus H. Hansen, Oscar C. González, Akshay Pujari, Luis de Lecea, Marco Quarta, Julie A. Kauer, Vivianne L. Tawfik

{"title":"Aging and injury drive neuronal senescence in the dorsal root ganglia","authors":"Lauren J. Donovan, Chelsie L. Brewer, Sabrina F. Bond, Alexander M. Laslavic, Aleishai Pena Lopez, Laura Colman, Claire E. Jordan, Linus H. Hansen, Oscar C. González, Akshay Pujari, Luis de Lecea, Marco Quarta, Julie A. Kauer, Vivianne L. Tawfik","doi":"10.1038/s41593-025-01954-x","DOIUrl":"https://doi.org/10.1038/s41593-025-01954-x","url":null,"abstract":"Aging negatively impacts central nervous system function; however, there is limited information about the cellular impact of aging on peripheral nervous system function. Importantly, injury to vulnerable peripheral axons of dorsal root ganglion (DRG) neurons results in somatosensory dysfunction, such as pain, at higher rates in aged individuals. Cellular senescence is common to both aging and injury and contributes to the aged pro-inflammatory environment. We discovered DRG neuron senescence in the context of aging and pain-inducing peripheral nerve injury in young (~3 months) and aged (~24 months) male and female mice. Senescent neurons were dynamic and heterogeneous in their expression of multiple senescence markers, including pro-inflammatory factor IL6. Senescence marker-expressing neurons had nociceptor-like profiles, included high-firing phenotypes and displayed increased excitability after IL6 application. Furthermore, elimination of senescent cells resulted in improvement of nociceptive behaviors in nerve-injured mice. Finally, male and female post-mortem human DRG contained senescent neurons that increased with age (~32 years old versus 65 years old). Overall, we describe a susceptibility of the peripheral nervous system to neuronal senescence—a potential targetable mechanism to treat sensory dysfunction, such as chronic pain, particularly in aged populations.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"1 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143946019","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 and non-CG DNA methylation stabilize the expression of long genes that distinguish closely related neuron types MeCP2和非cg DNA甲基化稳定了区分密切相关神经元类型的长基因的表达

IF 25 1区医学

Nature neuroscience Pub Date : 2025-05-12 DOI: 10.1038/s41593-025-01947-w

J. Russell Moore, Mati T. Nemera, Rinaldo D. D’Souza, Nicole Hamagami, Adam W. Clemens, Diana C. Beard, Alaina Urman, Yasmin Razia, Victoria Rodriguez Mendoza, Travis E. Law, John R. Edwards, Harrison W. Gabel

{"title":"MeCP2 and non-CG DNA methylation stabilize the expression of long genes that distinguish closely related neuron types","authors":"J. Russell Moore, Mati T. Nemera, Rinaldo D. D’Souza, Nicole Hamagami, Adam W. Clemens, Diana C. Beard, Alaina Urman, Yasmin Razia, Victoria Rodriguez Mendoza, Travis E. Law, John R. Edwards, Harrison W. Gabel","doi":"10.1038/s41593-025-01947-w","DOIUrl":"https://doi.org/10.1038/s41593-025-01947-w","url":null,"abstract":"The diversity of mammalian neurons is delineated by subtle gene expression differences that may require specialized mechanisms to be maintained. Neurons uniquely express the longest genes in the genome and use non-CG DNA methylation (mCA), together with the Rett syndrome protein methyl-CpG-binding protein 2 (MeCP2), to control gene expression. However, whether these distinctive gene structures and molecular machinery regulate neuronal diversity remains unexplored. Here, we use genomic and spatial transcriptomic analyses to show that MeCP2 maintains transcriptomic diversity across closely related neuron types. We uncover differential susceptibility of neuronal populations to MeCP2 loss according to global mCA levels and dissect methylation patterns driving shared and distinct MeCP2 gene regulation. We show that MeCP2 regulates long, mCA-enriched, ‘repeatedly tuned’ genes, that is, genes differentially expressed between many closely related neuron types, including across spatially distinct, vision-dependent gene programs in the visual cortex. Thus, MeCP2 maintains neuron type-specific gene programs to facilitate cellular diversity in the brain.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"5 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933509","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

Social rank modulates methamphetamine-seeking in dominant and subordinate male rodents via distinct dopaminergic pathways 社会等级通过不同的多巴胺能通路调节优势和从属雄性啮齿动物的甲基苯丙胺寻求

IF 25 1区医学

Nature neuroscience Pub Date : 2025-05-12 DOI: 10.1038/s41593-025-01951-0

Xiaofei Deng, Wei Xu, Yutong Liu, Haiyang Jing, Jiafeng Zhong, Kaige Sun, Ruiyi Zhou, Liang Xu, Xiaocong Wu, Baofang Zhang, Wanqi Chen, Shaolei Jiang, Gaowei Chen, Yingjie Zhu

{"title":"Social rank modulates methamphetamine-seeking in dominant and subordinate male rodents via distinct dopaminergic pathways","authors":"Xiaofei Deng, Wei Xu, Yutong Liu, Haiyang Jing, Jiafeng Zhong, Kaige Sun, Ruiyi Zhou, Liang Xu, Xiaocong Wu, Baofang Zhang, Wanqi Chen, Shaolei Jiang, Gaowei Chen, Yingjie Zhu","doi":"10.1038/s41593-025-01951-0","DOIUrl":"https://doi.org/10.1038/s41593-025-01951-0","url":null,"abstract":"Social status has a profound impact on mental health and propensity towards drug addiction. However, the neural mechanisms underlying the effects of social rank on drug-seeking behavior remain unclear. Here we found that dominant male rodents (based on the tube test) had denser mesocortical dopaminergic projections and were more resistant to methamphetamine (METH)-seeking, whereas subordinates had heightened dopaminergic function in the mesolimbic pathway and were more vulnerable to METH seeking. Optogenetic activation of the mesocortical dopaminergic pathway promoted winning and suppressed METH seeking in subordinates, whereas lesions of the mesocortical pathway increased METH seeking in dominants. Elevation of social rank with forced win training in subordinates led to remodeling of the dopaminergic system and prevented METH-seeking behavior. In females, however, both ranks were susceptible to METH seeking, with mesocorticolimbic pathways comparable to those in subordinate males. These results provide a framework for understanding the neural basis of the impact of social status on drug-seeking.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933508","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

Widespread brain–body integration during changes of arousal 在觉醒的变化中广泛的脑-体整合

IF 25 1区医学

Nature neuroscience Pub Date : 2025-05-09 DOI: 10.1038/s41593-025-01946-x

引用次数: 0

An energy blueprint of the human brain 人脑的能量蓝图

IF 25 1区医学

Nature neuroscience Pub Date : 2025-05-08 DOI: 10.1038/s41593-025-01967-6

Henrietta Howells

{"title":"An energy blueprint of the human brain","authors":"Henrietta Howells","doi":"10.1038/s41593-025-01967-6","DOIUrl":"https://doi.org/10.1038/s41593-025-01967-6","url":null,"abstract":"Functional neuroimaging enables measurement of brain organization and dynamics, but it only indirectly measures the subcellular bioenergetic processes that power brain activity. As such, there has been a gap between these large-scale imaging techniques and the microscopic scale of mitochondrial bioenergetics. In their study published in Nature, Mosharov and colleagues present a method to bridge this gap by creating a spatial map of mitochondrial diversity across the brain. They cut frozen human brain tissue into 3-mm cubes, comparable in size to MRI voxels, and then registered them to MNI space. They used advanced biochemical assays to profile mitochondrial distribution and function, which were then compared with standard brain-imaging data from different modalities. The findings revealed substantial heterogeneity in mitochondrial density and oxidative phosphorylation capacity between gray and white matter. The distribution of mitochondria is suggestive of a gradient that aligns with the phylogenetic development of the brain. This study offers insight into the energetic infrastructure that supports brain function, and it has the potential to inform research into healthy brain development and disease.Original reference: Nature https://doi.org/10.1038/s41586-025-08740-6 (2025)","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"117 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920805","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

Neuron subtypes play the long game 神经元亚型玩的是长期游戏

IF 25 1区医学

Nature neuroscience Pub Date : 2025-05-08 DOI: 10.1038/s41593-025-01968-5

Luis A. Mejia

{"title":"Neuron subtypes play the long game","authors":"Luis A. Mejia","doi":"10.1038/s41593-025-01968-5","DOIUrl":"https://doi.org/10.1038/s41593-025-01968-5","url":null,"abstract":"Approaches to assigning neurons to specific subtypes in the mouse brain are commonly based on electrophysiological, morphological and transcriptomic properties. Connectomic analyses for subtype classification have typically been restricted to electron microscopy datasets, but the authors of a study in Nature Methods instead leverage high-throughput single-neuron reconstruction datasets to classify cells on the basis of potential connectivity. The authors compiled a database of over 20,000 single-neuron morphological reconstructions and used machine learning to assign topologically connected axonal and dendritic arbors. Potential connectivity was therefore obtained from the overlap of dendritic and axonal arbor spatial domains. Importantly, classification of cells based on connectivity, or c-types, outperformed classification based on morphology, or conventional m-types, and substantially contributed to classification performance jointly with m-types. Further subtyping was possible using spatially correlated connectivity and morphological features. Using c-type classification, the authors were able to showcase subtyping of thalamic and thalamocortical neurons. Potential connectivity subtyping is thus a promising method by which to classify individual neurons in the brain into types.Original reference: Nat. Methods https://doi.org/10.1038/s41592-025-02621-6 (2025)","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"7 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920772","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

Stress and autophagy 应激和自噬

IF 25 1区医学

Nature neuroscience Pub Date : 2025-05-08 DOI: 10.1038/s41593-025-01969-4

Leonie Welberg

{"title":"Stress and autophagy","authors":"Leonie Welberg","doi":"10.1038/s41593-025-01969-4","DOIUrl":"https://doi.org/10.1038/s41593-025-01969-4","url":null,"abstract":"Stress disrupts homeostasis, and although various processes in the brain quickly restore equilibrium following acute stress, this is not the case during chronic stress, which can lead to depression. A paper published in Nature identifies autophagy as an important player in this phenomenon. The authors found that chronic stress in male mice downregulated autophagy in neurons in the lateral habenula (LHb) by increasing mTOR signaling. By contrast, acute stress increased autophagy in this area by increasing AMPK activation. Depression-like behavior in chronically stressed mice could be reversed or prevented by pharmacological activation of autophagy in the LHb. Various antidepressant drugs, including an mTOR inhibitor, required autophagy in this area to do their job. Autophagy mainly targeted postsynaptic glutamate receptors (GluRs) for degradation, and reduced autophagy — such as that in chronically stressed mice — was associated with excessive GluR expression and caused LHb neuron hyperactivity, impaired synaptic long-term depression, and depression-like behavior. Together, these findings show that autophagy is important for maintaining homeostasis in the LHb by counterbalancing the excessive GluRs upregulated by stress, and they suggest that restoring autophagy, possibly with an mTOR inhibitor, may be a promising target for antidepressant research.Original reference: Nature https://www.nature.com/articles/s41586-025-08807-4 (2025)","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"48 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920771","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

Sequential and independent probabilistic events regulate differential axon targeting during development in Drosophila melanogaster 顺序和独立的概率事件调节了黑腹果蝇发育过程中不同的轴突靶向

IF 25 1区医学

Nature neuroscience Pub Date : 2025-05-07 DOI: 10.1038/s41593-025-01937-y

Maheva Andriatsilavo, Carolina Barata, Eric Reifenstein, Alexandre Dumoulin, Tian Tao Griffin, Suchetana Bias Dutta, Esther T. Stoeckli, Max von Kleist, P. Robin Hiesinger, Bassem A. Hassan

{"title":"Sequential and independent probabilistic events regulate differential axon targeting during development in Drosophila melanogaster","authors":"Maheva Andriatsilavo, Carolina Barata, Eric Reifenstein, Alexandre Dumoulin, Tian Tao Griffin, Suchetana Bias Dutta, Esther T. Stoeckli, Max von Kleist, P. Robin Hiesinger, Bassem A. Hassan","doi":"10.1038/s41593-025-01937-y","DOIUrl":"https://doi.org/10.1038/s41593-025-01937-y","url":null,"abstract":"Variation in brain wiring contributes to non-heritable behavioral individuality. How and when these individualized wiring patterns emerge and stabilize during development remains unexplored. In this study, we investigated the axon targeting dynamics of Drosophila visual projecting neurons called DCNs/LC14s, using four-dimensional live-imaging, mathematical modeling and experimental validation. We found that alternative axon targeting choices are driven by a sequence of two independent genetically encoded stochastic processes. Early Notch lateral inhibition segregates DCNs into NotchON proximally targeting axons and NotchOFF axons that adopt a bi-potential transitory state. Subsequently, probabilistic accumulation of stable microtubules in a fraction of NotchOFF axons leads to distal target innervation, whereas the rest retract to adopt a NotchON target choice. The sequential wiring decisions result in the stochastic selection of different numbers of distally targeting axons in each individual. In summary, this work provides a conceptual and mechanistic framework for the emergence of individually variable, yet robust, circuit diagrams during development.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"31 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915720","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

Autonomic physiological coupling of the global fMRI signal 全局fMRI信号的自主生理耦合

IF 25 1区医学

Nature neuroscience Pub Date : 2025-05-07 DOI: 10.1038/s41593-025-01945-y

Taylor Bolt, Shiyu Wang, Jason S. Nomi, Roni Setton, Benjamin P. Gold, Blaise deB.Frederick, B. T. Thomas Yeo, J. Jean Chen, Dante Picchioni, Jeff H. Duyn, R. Nathan Spreng, Shella D. Keilholz, Lucina Q. Uddin, Catie Chang

{"title":"Autonomic physiological coupling of the global fMRI signal","authors":"Taylor Bolt, Shiyu Wang, Jason S. Nomi, Roni Setton, Benjamin P. Gold, Blaise deB.Frederick, B. T. Thomas Yeo, J. Jean Chen, Dante Picchioni, Jeff H. Duyn, R. Nathan Spreng, Shella D. Keilholz, Lucina Q. Uddin, Catie Chang","doi":"10.1038/s41593-025-01945-y","DOIUrl":"https://doi.org/10.1038/s41593-025-01945-y","url":null,"abstract":"The brain is closely attuned to visceral signals from the body’s internal environment, as evidenced by the numerous associations between neural, hemodynamic and peripheral physiological signals. Here we show that a major mode of these brain–body cofluctuations can be captured by a single spatiotemporal pattern. Across several independent samples, as well as single-echo and multi-echo functional magnetic resonance imaging (fMRI) data acquisition sequences, we identify widespread cofluctuations in the low-frequency range (0.01–0.1 Hz) between resting-state global fMRI signals, electroencephalogram (EEG) activity, and a host of peripheral autonomic signals spanning cardiovascular, pulmonary, exocrine and smooth muscle systems. The same brain–body cofluctuations observed at rest are elicited by cued deep breathing and intermittent sensory stimuli, as well as spontaneous phasic EEG events during sleep. Furthermore, we show that the spatial structure of global fMRI signals is maintained under experimental suppression of end-tidal carbon dioxide variations, suggesting that respiratory-driven fluctuations in arterial CO2 accompanying arousal cannot fully explain the origin of these signals in the brain. These findings suggest that the global fMRI signal is a substantial component of the arousal response governed by the autonomic nervous system.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"47 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915713","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: Dynamics of glia and neurons regulate homeostatic rest, sleep and feeding behavior in Drosophila 作者更正：神经胶质和神经元的动态调节果蝇的内稳态休息、睡眠和摄食行为

IF 25 1区医学

Nature neuroscience Pub Date : 2025-05-06 DOI: 10.1038/s41593-025-01984-5

Andres Flores-Valle, Ivan Vishniakou, Johannes D. Seelig

引用次数: 0