Nature neuroscience最新文献

α-Synuclein deposition in the kidney may contribute to Parkinson’s disease

IF 25 1区医学

Nature neuroscience Pub Date : 2025-01-23 DOI: 10.1038/s41593-024-01867-1

引用次数: 0

Propagation of pathologic α-synuclein from kidney to brain may contribute to Parkinson’s disease

IF 25 1区医学

Nature neuroscience Pub Date : 2025-01-23 DOI: 10.1038/s41593-024-01866-2

Xin Yuan, Shuke Nie, Yingxu Yang, Congcong Liu, Danhao Xia, Lanxia Meng, Yue Xia, Hua Su, Chun Zhang, Lihong Bu, Min Deng, Keqiang Ye, Jing Xiong, Liam Chen, Zhentao Zhang

{"title":"Propagation of pathologic α-synuclein from kidney to brain may contribute to Parkinson’s disease","authors":"Xin Yuan, Shuke Nie, Yingxu Yang, Congcong Liu, Danhao Xia, Lanxia Meng, Yue Xia, Hua Su, Chun Zhang, Lihong Bu, Min Deng, Keqiang Ye, Jing Xiong, Liam Chen, Zhentao Zhang","doi":"10.1038/s41593-024-01866-2","DOIUrl":"https://doi.org/10.1038/s41593-024-01866-2","url":null,"abstract":"The pathogenesis of Lewy body diseases (LBDs), including Parkinson’s disease (PD), involves α-synuclein (α-Syn) aggregation that originates in peripheral organs and spreads to the brain. PD incidence is increased in individuals with chronic renal failure, but the underlying mechanisms remain unknown. Here we observed α-Syn deposits in the kidneys of patients with LBDs and in the kidney and central nervous system of individuals with end-stage renal disease without documented LBDs. In male mice, we found that the kidney removes α-Syn from the blood, which is reduced in renal failure, causing α-Syn deposition in the kidney and subsequent spread into the brain. Intrarenal injection of α-Syn fibrils induces the propagation of α-Syn pathology from the kidney to the brain, which is blocked by renal denervation. Deletion of α-Syn in blood cells alleviates pathology in α-Syn A53T transgenic mice. Thus, the kidney may act as an initiation site for pathogenic α-Syn spread, and compromised renal function may contribute to the onset of LBDs.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"120 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020284","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

Mapping the cellular etiology of schizophrenia and complex brain phenotypes 绘制精神分裂症和复杂脑表型的细胞病因图谱

IF 25 1区医学

Nature neuroscience Pub Date : 2025-01-20 DOI: 10.1038/s41593-024-01834-w

Laramie E. Duncan, Tayden Li, Madeleine Salem, Will Li, Leili Mortazavi, Hazal Senturk, Naghmeh Shahverdizadeh, Sam Vesuna, Hanyang Shen, Jong Yoon, Gordon Wang, Jacob Ballon, Longzhi Tan, Brandon Scott Pruett, Brian Knutson, Karl Deisseroth, William J. Giardino

{"title":"Mapping the cellular etiology of schizophrenia and complex brain phenotypes","authors":"Laramie E. Duncan, Tayden Li, Madeleine Salem, Will Li, Leili Mortazavi, Hazal Senturk, Naghmeh Shahverdizadeh, Sam Vesuna, Hanyang Shen, Jong Yoon, Gordon Wang, Jacob Ballon, Longzhi Tan, Brandon Scott Pruett, Brian Knutson, Karl Deisseroth, William J. Giardino","doi":"10.1038/s41593-024-01834-w","DOIUrl":"https://doi.org/10.1038/s41593-024-01834-w","url":null,"abstract":"Psychiatric disorders are multifactorial and effective treatments are lacking. Probable contributing factors to the challenges in therapeutic development include the complexity of the human brain and the high polygenicity of psychiatric disorders. Combining well-powered genome-wide and brain-wide genetics and transcriptomics analyses can deepen our understanding of the etiology of psychiatric disorders. Here, we leverage two landmark resources to infer the cell types involved in the etiology of schizophrenia, other psychiatric disorders and informative comparison of brain phenotypes. We found both cortical and subcortical neuronal associations for schizophrenia, bipolar disorder and depression. These cell types included somatostatin interneurons, excitatory neurons from the retrosplenial cortex and eccentric medium spiny-like neurons from the amygdala. In contrast we found T cell and B cell associations with multiple sclerosis and microglial associations with Alzheimer’s disease. We provide a framework for a cell-type-based classification system that can lead to drug repurposing or development opportunities and personalized treatments. This work formalizes a data-driven, cellular and molecular model of complex brain disorders.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"69 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989984","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

Propagation of neuronal micronuclei regulates microglial characteristics

IF 25 1区医学

Nature neuroscience Pub Date : 2025-01-17 DOI: 10.1038/s41593-024-01863-5

Sarasa Yano, Natsu Asami, Yusuke Kishi, Ikuko Takeda, Hikari Kubotani, Yuki Hattori, Ayako Kitazawa, Kanehiro Hayashi, Ken-ichiro Kubo, Mai Saeki, Chihiro Maeda, Chihiro Hiraki, Rin-ichiro Teruya, Takumi Taketomi, Kaito Akiyama, Tomomi Okajima-Takahashi, Ban Sato, Hiroaki Wake, Yukiko Gotoh, Kazunori Nakajima, Takeshi Ichinohe, Takeshi Nagata, Tomoki Chiba, Fuminori Tsuruta

{"title":"Propagation of neuronal micronuclei regulates microglial characteristics","authors":"Sarasa Yano, Natsu Asami, Yusuke Kishi, Ikuko Takeda, Hikari Kubotani, Yuki Hattori, Ayako Kitazawa, Kanehiro Hayashi, Ken-ichiro Kubo, Mai Saeki, Chihiro Maeda, Chihiro Hiraki, Rin-ichiro Teruya, Takumi Taketomi, Kaito Akiyama, Tomomi Okajima-Takahashi, Ban Sato, Hiroaki Wake, Yukiko Gotoh, Kazunori Nakajima, Takeshi Ichinohe, Takeshi Nagata, Tomoki Chiba, Fuminori Tsuruta","doi":"10.1038/s41593-024-01863-5","DOIUrl":"https://doi.org/10.1038/s41593-024-01863-5","url":null,"abstract":"Microglia—resident immune cells in the central nervous system—undergo morphological and functional changes in response to signals from the local environment and mature into various homeostatic states. However, niche signals underlying microglial differentiation and maturation remain unknown. Here, we show that neuronal micronuclei (MN) transfer to microglia, which is followed by changing microglial characteristics during the postnatal period. Neurons passing through a dense region of the developing neocortex give rise to MN and release them into the extracellular space, before being incorporated into microglia and inducing morphological changes. Two-photon imaging analyses have revealed that microglia incorporating MN tend to slowly retract their processes. Loss of the cGAS gene alleviates effects on micronucleus-dependent morphological changes. Neuronal MN-harboring microglia also exhibit unique transcriptome signatures. These results demonstrate that neuronal MN serve as niche signals that transform microglia, and provide a potential mechanism for regulation of microglial characteristics in the early postnatal neocortex.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"95 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987662","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

Dynamical constraints on neural population activity

IF 25 1区医学

Nature neuroscience Pub Date : 2025-01-17 DOI: 10.1038/s41593-024-01845-7

Emily R. Oby, Alan D. Degenhart, Erinn M. Grigsby, Asma Motiwala, Nicole T. McClain, Patrick J. Marino, Byron M. Yu, Aaron P. Batista

引用次数: 0

Neural populations are dynamic but constrained

IF 25 1区医学

Nature neuroscience Pub Date : 2025-01-17 DOI: 10.1038/s41593-024-01793-2

Amy L. Orsborn

引用次数: 0

Neural mechanisms of relational learning and fast knowledge reassembly in plastic neural networks

IF 25 1区医学

Nature neuroscience Pub Date : 2025-01-15 DOI: 10.1038/s41593-024-01852-8

Thomas Miconi, Kenneth Kay

{"title":"Neural mechanisms of relational learning and fast knowledge reassembly in plastic neural networks","authors":"Thomas Miconi, Kenneth Kay","doi":"10.1038/s41593-024-01852-8","DOIUrl":"https://doi.org/10.1038/s41593-024-01852-8","url":null,"abstract":"Humans and animals have a striking ability to learn relationships between items in experience (such as stimuli, objects and events), enabling structured generalization and rapid assimilation of new information. A fundamental type of such relational learning is order learning, which enables transitive inference (if A > B and B > C, then A > C) and list linking (A > B > C and D > E > F rapidly ‘reassembled’ into A > B > C > D > E > F upon learning C > D). Despite longstanding study, a neurobiologically plausible mechanism for transitive inference and rapid reassembly of order knowledge has remained elusive. Here we report that neural networks endowed with neuromodulated synaptic plasticity (allowing for self-directed learning) and identified through artificial metalearning (learning-to-learn) are able to perform both transitive inference and list linking and, further, express behavioral patterns widely observed in humans and animals. Crucially, only networks that adopt an ‘active’ solution, in which items from past trials are reinstated in neural activity in recoded form, are capable of list linking. These results identify fully neural mechanisms for relational learning, and highlight a method for discovering such mechanisms.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"26 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981686","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

A distinct hypothalamus–habenula circuit governs risk preference

IF 25 1区医学

Nature neuroscience Pub Date : 2025-01-08 DOI: 10.1038/s41593-024-01856-4

Dominik Groos, Anna Maria Reuss, Peter Rupprecht, Tevye Stachniak, Christopher Lewis, Shuting Han, Adrian Roggenbach, Oliver Sturman, Yaroslav Sych, Martin Wieckhorst, Johannes Bohacek, Theofanis Karayannis, Adriano Aguzzi, Fritjof Helmchen

{"title":"A distinct hypothalamus–habenula circuit governs risk preference","authors":"Dominik Groos, Anna Maria Reuss, Peter Rupprecht, Tevye Stachniak, Christopher Lewis, Shuting Han, Adrian Roggenbach, Oliver Sturman, Yaroslav Sych, Martin Wieckhorst, Johannes Bohacek, Theofanis Karayannis, Adriano Aguzzi, Fritjof Helmchen","doi":"10.1038/s41593-024-01856-4","DOIUrl":"https://doi.org/10.1038/s41593-024-01856-4","url":null,"abstract":"Appropriate risk evaluation is essential for survival in complex, uncertain environments. Confronted with choosing between certain (safe) and uncertain (risky) options, animals show strong preference for either option consistently across extended time periods. How such risk preference is encoded in the brain remains elusive. A candidate region is the lateral habenula (LHb), which is prominently involved in value-guided behavior. Here, using a balanced two-alternative choice task and longitudinal two-photon calcium imaging in mice, we identify risk-preference-selective activity in LHb neurons reflecting individual risk preference before action selection. By using whole-brain anatomical tracing, multi-fiber photometry and projection-specific and cell-type-specific optogenetics, we find glutamatergic LHb projections from the medial (MH) but not lateral (LH) hypothalamus providing behavior-relevant synaptic input before action selection. Optogenetic stimulation of MH→LHb axons evoked excitatory and inhibitory postsynaptic responses, whereas LH→LHb projections were excitatory. We thus reveal functionally distinct hypothalamus–habenula circuits for risk preference in habitual economic decision-making.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"35 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935892","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

Together but opposites in reward

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-01-08 DOI: 10.1038/s41593-024-01861-7

Luis A. Mejia

引用次数: 0

Glioblastoma–neuron networks

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-01-08 DOI: 10.1038/s41593-024-01862-6

Shari Wiseman

引用次数: 0