Nature neuroscience最新文献_第8页

Neural ensembles that encode nocifensive mechanical and heat pain in mouse spinal cord 小鼠脊髓中编码有害机械痛和热痛的神经系统

IF 25 1区医学

Nature neuroscience Pub Date : 2025-03-24 DOI: 10.1038/s41593-025-01921-6

Ming-Dong Zhang, Jussi Kupari, Jie Su, Kajsa A. Magnusson, Yizhou Hu, Laura Calvo-Enrique, Dmitry Usoskin, Gioele W. Albisetti, Mikaela M. Ceder, Katharina Henriksson, Andrew D. Leavitt, Hanns Ulrich Zeilhofer, Tomas Hökfelt, Malin C. Lagerström, Patrik Ernfors

{"title":"Neural ensembles that encode nocifensive mechanical and heat pain in mouse spinal cord","authors":"Ming-Dong Zhang, Jussi Kupari, Jie Su, Kajsa A. Magnusson, Yizhou Hu, Laura Calvo-Enrique, Dmitry Usoskin, Gioele W. Albisetti, Mikaela M. Ceder, Katharina Henriksson, Andrew D. Leavitt, Hanns Ulrich Zeilhofer, Tomas Hökfelt, Malin C. Lagerström, Patrik Ernfors","doi":"10.1038/s41593-025-01921-6","DOIUrl":"https://doi.org/10.1038/s41593-025-01921-6","url":null,"abstract":"Acute pain is an unpleasant experience caused by noxious stimuli. How the spinal neural circuits attribute differences in quality of noxious information remains unknown. By means of genetic capturing, activity manipulation and single-cell RNA sequencing, we identified distinct neural ensembles in the adult mouse spinal cord encoding mechanical and heat pain. Reactivation or silencing of these ensembles potentiated or stopped, respectively, paw shaking, lifting and licking within but not across the stimuli modalities. Within ensembles, polymodal Gal+ inhibitory neurons with monosynaptic contacts to A-fiber sensory neurons gated pain transmission independent of modality. Peripheral nerve injury led to inferred microglia-driven inflammation and an ensemble transition with decreased recruitment of Gal+ inhibitory neurons and increased excitatory drive. Forced activation of Gal+ neurons reversed hypersensitivity associated with neuropathy. Our results reveal the existence of a spinal representation that forms the neural basis of the discriminative and defensive qualities of acute pain, and these neurons are under the control of a shared feed-forward inhibition.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"123 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677654","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

Phase of firing does not reflect temporal order in sequence memory of humans and recurrent neural networks 放电的相位不反映人类序列记忆和循环神经网络的时间顺序

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-03-24 DOI: 10.1038/s41593-025-01893-7

Stefanie Liebe, Johannes Niediek, Matthijs Pals, Thomas P. Reber, Jennifer Faber, Jan Boström, Christian E. Elger, Jakob H. Macke, Florian Mormann

{"title":"Phase of firing does not reflect temporal order in sequence memory of humans and recurrent neural networks","authors":"Stefanie Liebe, Johannes Niediek, Matthijs Pals, Thomas P. Reber, Jennifer Faber, Jan Boström, Christian E. Elger, Jakob H. Macke, Florian Mormann","doi":"10.1038/s41593-025-01893-7","DOIUrl":"10.1038/s41593-025-01893-7","url":null,"abstract":"The temporal order of a sequence of events has been thought to be reflected in the ordered firing of neurons at different phases of theta oscillations. Here we assess this by measuring single neuron activity (1,420 neurons) and local field potentials (921 channels) in the medial temporal lobe of 16 patients with epilepsy performing a working-memory task for temporal order. During memory maintenance, we observe theta oscillations, preferential firing of single neurons to theta phase and a close relationship between phase of firing and item position. However, the firing order did not match item order. Training recurrent neural networks to perform an analogous task, we also show the generation of theta oscillations, theta phase-dependent firing related to item position and, again, no match between firing and item order. Rather, our results suggest a mechanistic link between phase order, stimulus timing and oscillation frequency. In both biological and artificial neural networks, we provide evidence supporting the role of phase of firing in working-memory processing. The temporal order of events in working memory is thought to be reflected by ordered neuronal firing at different phases. Here the authors show that this is not the case and that phase order is linked to stimulus timing and oscillation frequency.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 4","pages":"873-882"},"PeriodicalIF":21.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-025-01893-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677869","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

Integrating multimodal data to understand cortical circuit architecture and function 整合多模态数据以了解皮质电路的结构和功能

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-03-24 DOI: 10.1038/s41593-025-01904-7

Anton Arkhipov, Nuno da Costa, Saskia de Vries, Trygve Bakken, Corbett Bennett, Amy Bernard, Jim Berg, Michael Buice, Forrest Collman, Tanya Daigle, Marina Garrett, Nathan Gouwens, Peter A. Groblewski, Julie Harris, Michael Hawrylycz, Rebecca Hodge, Tim Jarsky, Brian Kalmbach, Jerome Lecoq, Brian Lee, Ed Lein, Boaz Levi, Stefan Mihalas, Lydia Ng, Shawn Olsen, Clay Reid, Joshua H. Siegle, Staci Sorensen, Bosiljka Tasic, Carol Thompson, Jonathan T. Ting, Cindy van Velthoven, Shenqin Yao, Zizhen Yao, Christof Koch, Hongkui Zeng

{"title":"Integrating multimodal data to understand cortical circuit architecture and function","authors":"Anton Arkhipov, Nuno da Costa, Saskia de Vries, Trygve Bakken, Corbett Bennett, Amy Bernard, Jim Berg, Michael Buice, Forrest Collman, Tanya Daigle, Marina Garrett, Nathan Gouwens, Peter A. Groblewski, Julie Harris, Michael Hawrylycz, Rebecca Hodge, Tim Jarsky, Brian Kalmbach, Jerome Lecoq, Brian Lee, Ed Lein, Boaz Levi, Stefan Mihalas, Lydia Ng, Shawn Olsen, Clay Reid, Joshua H. Siegle, Staci Sorensen, Bosiljka Tasic, Carol Thompson, Jonathan T. Ting, Cindy van Velthoven, Shenqin Yao, Zizhen Yao, Christof Koch, Hongkui Zeng","doi":"10.1038/s41593-025-01904-7","DOIUrl":"10.1038/s41593-025-01904-7","url":null,"abstract":"In recent years there has been a tremendous growth in new technologies that allow large-scale investigation of different characteristics of the nervous system at an unprecedented level of detail. There is a growing trend to use combinations of these new techniques to determine direct links between different modalities. In this Perspective, we focus on the mouse visual cortex, as this is one of the model systems in which much progress has been made in the integration of multimodal data to advance understanding. We review several approaches that allow integration of data regarding various properties of cortical cell types, connectivity at the level of brain areas, cell types and individual cells, and functional neural activity in vivo. The increasingly crucial contributions of computation and theory in analyzing and systematically modeling data are also highlighted. Together with open sharing of data, tools and models, integrative approaches are essential tools in modern neuroscience for improving our understanding of the brain architecture, mechanisms and function. This paper discusses how experimental and computational studies integrating multimodal data, such as RNA expression, connectivity and neural activity, are advancing our understanding of the architecture, mechanisms and function of cortical circuits.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 4","pages":"717-730"},"PeriodicalIF":21.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677656","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: Mitochondrial respiratory complex IV deficiency recapitulates amyotrophic lateral sclerosis 作者更正：线粒体呼吸复合体 IV 缺乏症再现肌萎缩侧索硬化症

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-03-21 DOI: 10.1038/s41593-025-01941-2

Man Cheng, Dan Lu, Kexin Li, Yan Wang, Xiwen Tong, Xiaolong Qi, Chuanzhu Yan, Kunqian Ji, Junlin Wang, Wei Wang, Huijiao Lv, Xu Zhang, Weining Kong, Jian Zhang, Jiaxin Ma, Keru Li, Yaheng Wang, Jingyu Feng, Panpan Wei, Qiushuang Li, Chengyong Shen, Xiang-Dong Fu, Yuanwu Ma, Xiaorong Zhang

引用次数: 0

Cancer research needs neuroscience and neuroscientists 癌症研究需要神经科学和神经科学家

IF 25 1区医学

Nature neuroscience Pub Date : 2025-03-20 DOI: 10.1038/s41593-025-01925-2

Michelle Monje, Frank Winkler

引用次数: 0

Synaptic plasticity rules driving representational shifting in the hippocampus 突触可塑性规则驱动海马体的表征转移

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-03-20 DOI: 10.1038/s41593-025-01894-6

Antoine D. Madar, Anqi Jiang, Can Dong, Mark E. J. Sheffield

{"title":"Synaptic plasticity rules driving representational shifting in the hippocampus","authors":"Antoine D. Madar, Anqi Jiang, Can Dong, Mark E. J. Sheffield","doi":"10.1038/s41593-025-01894-6","DOIUrl":"10.1038/s41593-025-01894-6","url":null,"abstract":"Synaptic plasticity is widely thought to support memory storage in the brain, but the rules determining impactful synaptic changes in vivo are not known. We considered the trial-by-trial shifting dynamics of hippocampal place fields (PF) as an indicator of ongoing plasticity during memory formation and familiarization. By implementing different plasticity rules in computational models of spiking place cells and comparing them to experimentally measured PFs from mice navigating familiar and new environments, we found that behavioral timescale synaptic plasticity (BTSP), rather than Hebbian spike-timing-dependent plasticity (STDP), best explains PF shifting dynamics. BTSP-triggering events are rare, but more frequent during new experiences. During exploration, their probability is dynamic—it decays after PF onset, but continually drives a population-level representational drift. Additionally, our results show that BTSP occurs in CA3 but is less frequent and phenomenologically different than in CA1. Overall, our study provides a new framework to understand how synaptic plasticity continuously shapes neuronal representations during learning. Madar et al. report that behavioral timescale synaptic plasticity (BTSP), not spike-timing-dependent plasticity, explains heterogeneous place fields shifting in the hippocampus. The probability of BTSP induction follows patterned dynamics, is higher in new contexts and lower in CA3 than CA1.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 4","pages":"848-860"},"PeriodicalIF":21.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660550","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

Prospective contingency explains behavior and dopamine signals during associative learning 前瞻性偶然性解释了联想学习过程中的行为和多巴胺信号

IF 25 1区医学

Nature neuroscience Pub Date : 2025-03-18 DOI: 10.1038/s41593-025-01915-4

Lechen Qian, Mark Burrell, Jay A. Hennig, Sara Matias, Venkatesh N. Murthy, Samuel J. Gershman, Naoshige Uchida

{"title":"Prospective contingency explains behavior and dopamine signals during associative learning","authors":"Lechen Qian, Mark Burrell, Jay A. Hennig, Sara Matias, Venkatesh N. Murthy, Samuel J. Gershman, Naoshige Uchida","doi":"10.1038/s41593-025-01915-4","DOIUrl":"https://doi.org/10.1038/s41593-025-01915-4","url":null,"abstract":"Associative learning depends on contingency, the degree to which a stimulus predicts an outcome. Despite its importance, the neural mechanisms linking contingency to behavior remain elusive. In the present study, we examined the dopamine activity in the ventral striatum—a signal implicated in associative learning—in a Pavlovian contingency degradation task in mice. We show that both anticipatory licking and dopamine responses to a conditioned stimulus decreased when additional rewards were delivered uncued, but remained unchanged if additional rewards were cued. These results conflict with contingency-based accounts using a traditional definition of contingency or a new causal learning model (ANCCR), but can be explained by temporal difference (TD) learning models equipped with an appropriate intertrial interval state representation. Recurrent neural networks trained within a TD framework develop state representations akin to our best ‘handcrafted’ model. Our findings suggest that the TD error can be a measure that describes both contingency and dopaminergic activity.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"6 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640387","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

Composing hippocampal maps from cortical building blocks in replay 重放过程中由皮层构建块组成海马图

IF 25 1区医学

Nature neuroscience Pub Date : 2025-03-18 DOI: 10.1038/s41593-025-01909-2

引用次数: 0

Lewy body disease can spread via two distinct body-first routes 路易体病可通过两种不同的身体优先途径传播

IF 25 1区医学

Nature neuroscience Pub Date : 2025-03-18 DOI: 10.1038/s41593-025-01911-8

引用次数: 0

Endothelial TDP-43 depletion disrupts core blood–brain barrier pathways in neurodegeneration 内皮细胞TDP-43耗竭破坏神经退行性变的核心血脑屏障通路

IF 25 1区医学

Nature neuroscience Pub Date : 2025-03-14 DOI: 10.1038/s41593-025-01914-5

Omar M. F. Omar, Amy L. Kimble, Ashok Cheemala, Jordan D. Tyburski, Swati Pandey, Qian Wu, Bo Reese, Evan R. Jellison, Bing Hao, Yunfeng Li, Riqiang Yan, Patrick A. Murphy

{"title":"Endothelial TDP-43 depletion disrupts core blood–brain barrier pathways in neurodegeneration","authors":"Omar M. F. Omar, Amy L. Kimble, Ashok Cheemala, Jordan D. Tyburski, Swati Pandey, Qian Wu, Bo Reese, Evan R. Jellison, Bing Hao, Yunfeng Li, Riqiang Yan, Patrick A. Murphy","doi":"10.1038/s41593-025-01914-5","DOIUrl":"https://doi.org/10.1038/s41593-025-01914-5","url":null,"abstract":"Endothelial cells (ECs) help maintain the blood–brain barrier but deteriorate in many neurodegenerative disorders. Here we show, using a specialized method to isolate EC and microglial nuclei from postmortem human cortex (92 donors, 50 male and 42 female, aged 20–98 years), that intranuclear cellular indexing of transcriptomes and epitopes enables simultaneous profiling of nuclear proteins and RNA transcripts at a single-nucleus resolution. We identify a disease-associated subset of capillary ECs in Alzheimer’s disease, amyotrophic lateral sclerosis and frontotemporal degeneration. These capillaries exhibit reduced nuclear β-catenin and β-catenin-downstream genes, along with elevated TNF/NF-κB markers. Notably, these transcriptional changes correlate with the loss of nuclear TDP-43, an RNA-binding protein also depleted in neuronal nuclei. TDP-43 disruption in human and mouse ECs replicates these alterations, suggesting that TDP-43 deficiency in ECs is an important factor contributing to blood–brain barrier breakdown in neurodegenerative diseases.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"18 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618762","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