Nature neuroscience最新文献_第3页

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

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Cancer research needs neuroscience and neuroscientists

IF 25 1区医学

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

Michelle Monje, Frank Winkler

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Synaptic plasticity rules driving representational shifting in the hippocampus

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}

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Prospective contingency explains behavior and dopamine signals during associative learning

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

IF 25 1区医学

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

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Lewy body disease can spread via two distinct body-first routes

IF 25 1区医学

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

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Endothelial TDP-43 depletion disrupts core blood–brain barrier pathways in neurodegeneration

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

Sympathetic and parasympathetic subtypes of body-first Lewy body disease observed in postmortem tissue from prediagnostic individuals

IF 25 1区医学

Nature neuroscience Pub Date : 2025-03-13 DOI: 10.1038/s41593-025-01910-9

Katrine B. Andersen, Anushree Krishnamurthy, Mie Kristine Just, Nathalie Van Den Berge, Casper Skjærbæk, Jacob Horsager, Karoline Knudsen, Jacob W. Vogel, Jon B. Toledo, Johannes Attems, Tuomo Polvikoski, Yuko Saito, Shigeo Murayama, Per Borghammer

{"title":"Sympathetic and parasympathetic subtypes of body-first Lewy body disease observed in postmortem tissue from prediagnostic individuals","authors":"Katrine B. Andersen, Anushree Krishnamurthy, Mie Kristine Just, Nathalie Van Den Berge, Casper Skjærbæk, Jacob Horsager, Karoline Knudsen, Jacob W. Vogel, Jon B. Toledo, Johannes Attems, Tuomo Polvikoski, Yuko Saito, Shigeo Murayama, Per Borghammer","doi":"10.1038/s41593-025-01910-9","DOIUrl":"https://doi.org/10.1038/s41593-025-01910-9","url":null,"abstract":"Recent studies suggest the existence of brain-first and body-first subtypes within the Lewy body disorder (LBD) spectrum, including Parkinson’s disease. These studies primarily focused on α-synuclein propagation through the parasympathetic vagal and olfactory bulb routes, leaving the possibility of a sympathetic nervous system spreading route unexplored. In the present study, we analyzed two postmortem datasets, which included 173 and 129 cases positive for Lewy pathology. We observed a clear distinction between brain-first and body-first subtypes in early prediagnostic cases with mild Lewy pathology. Brain-first cases displayed minimal peripheral organ pathology in prediagnostic phases, contrasting with marked autonomic involvement in prediagnostic body-first cases. Utilizing the SuStaIn machine learning algorithm, we identified two distinct body-first subtypes, one with vagal predominance and another with sympathetic predominance, in equal proportions. Our study supports the existence of three prediagnostic LBD subtypes and highlights the sympathetic nervous system alongside the parasympathetic system in LBD onset and progression.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"19 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607985","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

Expectation-driven sensory adaptations support enhanced acuity during categorical perception

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-03-13 DOI: 10.1038/s41593-025-01899-1

Tim Sainburg, Trevor S. McPherson, Ezequiel M. Arneodo, Srihita Rudraraju, Michael Turvey, Bradley H. Theilman, Pablo Tostado Marcos, Marvin Thielk, Timothy Q. Gentner

{"title":"Expectation-driven sensory adaptations support enhanced acuity during categorical perception","authors":"Tim Sainburg, Trevor S. McPherson, Ezequiel M. Arneodo, Srihita Rudraraju, Michael Turvey, Bradley H. Theilman, Pablo Tostado Marcos, Marvin Thielk, Timothy Q. Gentner","doi":"10.1038/s41593-025-01899-1","DOIUrl":"10.1038/s41593-025-01899-1","url":null,"abstract":"Expectations can influence perception in seemingly contradictory ways, either by directing attention to expected stimuli and enhancing perceptual acuity or by stabilizing perception and diminishing acuity within expected stimulus categories. The neural mechanisms supporting these dual roles of expectation are not well understood. Here, we trained European starlings to classify ambiguous song syllables in both expected and unexpected acoustic contexts. We show that birds employ probabilistic, Bayesian integration to classify syllables, leveraging their expectations to stabilize their perceptual behavior. However, auditory sensory neural populations do not reflect this integration. Instead, expectation enhances the acuity of auditory sensory neurons in high-probability regions of the stimulus space. This modulation diverges from patterns typically observed in motor areas, where Bayesian integration of sensory inputs and expectations predominates. Our results suggest that peripheral sensory systems use expectation to improve sensory representations and maintain high-fidelity representations of the world, allowing downstream circuits to flexibly integrate this information with expectations to drive behavior. Bayesian models explain how context biases perceptual behavior toward expected categories, but sensory neurons do not reflect this bias. Instead, expectation sharpens sensory acuity, independent of downstream decision making.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 4","pages":"861-872"},"PeriodicalIF":21.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607986","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 axonal brake on striatal dopamine output by cholinergic interneurons 胆碱能中间神经元对纹状体多巴胺输出的轴突制动作用

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-03-13 DOI: 10.1038/s41593-025-01906-5

Yan-Feng Zhang, Pengwei Luan, Qinbo Qiao, Yiran He, Peter Zatka-Haas, Guofeng Zhang, Michael Z. Lin, Armin Lak, Miao Jing, Edward O. Mann, Stephanie J. Cragg

{"title":"An axonal brake on striatal dopamine output by cholinergic interneurons","authors":"Yan-Feng Zhang, Pengwei Luan, Qinbo Qiao, Yiran He, Peter Zatka-Haas, Guofeng Zhang, Michael Z. Lin, Armin Lak, Miao Jing, Edward O. Mann, Stephanie J. Cragg","doi":"10.1038/s41593-025-01906-5","DOIUrl":"10.1038/s41593-025-01906-5","url":null,"abstract":"Depolarization of axons is necessary for somatic action potentials to trigger axonal neurotransmitter release. Here we show that striatal cholinergic interneurons (ChIs) and nicotinic receptors (nAChRs) on mouse dopamine axons interrupt this relationship. After nAChR-mediated depolarization, dopamine release by subsequent depolarization events was suppressed for ~100 ms. This suppression was not due to depletion of dopamine or acetylcholine, but to a limited reactivation of dopamine axons after nAChR-mediated depolarization, and is more prominent in dorsal than in ventral striatum. In vivo, nAChRs predominantly depressed dopamine release, as nAChR antagonism in dorsal striatum elevated dopamine detected with optic-fiber photometry of dopamine sensor GRABDA2m and promoted conditioned place preference. Our findings reveal that ChIs acting via nAChRs transiently limit the reactivation of dopamine axons for subsequent action potentials in dopamine neurons and therefore generate a dynamic inverse scaling of dopamine release according to ChI activity. Cholinergic interneurons act at nicotinic receptors to depress dopamine release, interrupting its relationship to dopamine neuron firing and supporting an inverse scaling of dopamine release according to cholinergic activity.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 4","pages":"783-794"},"PeriodicalIF":21.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-025-01906-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607987","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