Neuron最新文献

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A neural basis for distinguishing imagination from reality. 区分想象和现实的神经基础。
IF 14.7 1区 医学
Neuron Pub Date : 2025-05-30 DOI: 10.1016/j.neuron.2025.05.015
Nadine Dijkstra, Thomas von Rein, Peter Kok, Stephen M Fleming
{"title":"A neural basis for distinguishing imagination from reality.","authors":"Nadine Dijkstra, Thomas von Rein, Peter Kok, Stephen M Fleming","doi":"10.1016/j.neuron.2025.05.015","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.05.015","url":null,"abstract":"<p><p>Humans are able to imagine scenarios that are decoupled from the current environment by internally activating perceptual representations. Although an efficient re-use of existing resources, it remains unknown how human observers classify perceptual signals as reflecting external reality, as opposed to internal simulation or imagination. Here, we show that judgments of reality are underpinned by the combined strength of sensory activity generated by either imagery or perception in the fusiform gyrus. Activity fluctuations in this region predict confusions between imagery and perception on a trial-by-trial basis and interact with a frontal brain network encoding binary judgments of reality. Our results demonstrate that a key mechanism through which the brain distinguishes imagination from reality is by monitoring the activity of the mid-level visual cortex. These findings increase our understanding of failures of reality testing and lay the foundations for characterizing a generalized perceptual reality monitoring system in the human brain.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248971","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
Grouping signals in primate visual cortex. 灵长类动物视觉皮层的分组信号。
IF 14.7 1区 医学
Neuron Pub Date : 2025-05-29 DOI: 10.1016/j.neuron.2025.05.003
Tom P Franken, John H Reynolds
{"title":"Grouping signals in primate visual cortex.","authors":"Tom P Franken, John H Reynolds","doi":"10.1016/j.neuron.2025.05.003","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.05.003","url":null,"abstract":"<p><p>Our understanding of scenes as organized collections of objects is remarkably stable despite eye movements. This may be due, in part, to neurons in area V2 that signal which side of a border is foreground (border ownership [BOS]) for hundreds of milliseconds after the defining information is deleted, and this signal transfers with eye movements. The grouping model explains this through a hypothetical short-latency grouping signal downstream. This would be a persistent pattern of preferred ownership toward the center of the receptive field, which also occurs de novo after eye movements. Our recordings identify such a grouping signal in macaque V4, which occurs fast enough to underlie BOS in V2. These V4 neurons are not as strongly tuned for contrast polarity as are BOS neurons. This suggests a division of labor in which grouping signals provide spatiotemporal continuity of segmented surfaces, whereas BOS neurons link this with feature information.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216417","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
Identification of the velum interpositum as a meningeal-CNS route for myeloid cell trafficking into the brain. 鉴别膜间质作为髓细胞进入脑的脑膜-中枢神经系统通路。
IF 14.7 1区 医学
Neuron Pub Date : 2025-05-28 DOI: 10.1016/j.neuron.2025.05.004
Lindsay A Hohsfield, Sung Jin Kim, Rocio A Barahona, Caden M Henningfield, Kimiya Mansour, Kristen D Vallejo, Kate I Tsourmas, Nellie E Kwang, Yasamine Ghorbanian, Julio Alejandro Ayala Angulo, Pan Gao, Collin Pachow, Matthew A Inlay, Craig M Walsh, Xiangmin Xu, Thomas E Lane, Kim N Green
{"title":"Identification of the velum interpositum as a meningeal-CNS route for myeloid cell trafficking into the brain.","authors":"Lindsay A Hohsfield, Sung Jin Kim, Rocio A Barahona, Caden M Henningfield, Kimiya Mansour, Kristen D Vallejo, Kate I Tsourmas, Nellie E Kwang, Yasamine Ghorbanian, Julio Alejandro Ayala Angulo, Pan Gao, Collin Pachow, Matthew A Inlay, Craig M Walsh, Xiangmin Xu, Thomas E Lane, Kim N Green","doi":"10.1016/j.neuron.2025.05.004","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.05.004","url":null,"abstract":"<p><p>The borders of the central nervous system (CNS) host a repertoire of immune cells and mediate critical neuroimmune interactions, including the infiltration of peripheral myeloid cells into the CNS. Despite the fundamental role of leukocyte infiltration under physiological and pathological conditions, the neuroanatomical route of cell entry into the brain remains unclear. Here, we describe a specialized structure underneath the hippocampus, the velum interpositum (VI), that serves as a site for myeloid cell entry into the CNS. The VI functions as an extra-parenchymal leptomeningeal extension containing distinct myeloid cells subsets. Fate-mapping studies confirm meningeal and peripheral myeloid cell occupancy within the VI. Additionally, we highlight the distinct use of this route in the developing, irradiated, and demyelinating disease brain, indicating that myeloid cell trafficking through the VI could have important clinical implications for neurological disease.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226084","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
Spatiotemporal transcriptomic maps of mouse intracerebral hemorrhage at single-cell resolution. 单细胞分辨率下小鼠脑出血的时空转录组图。
IF 14.7 1区 医学
Neuron Pub Date : 2025-05-23 DOI: 10.1016/j.neuron.2025.04.026
Rong Xiang, Junmin Wang, Zhan Chen, Jin Tao, Qinfeng Peng, Ruoqi Ding, Tao Zhou, Zhencheng Tu, Shaoshuai Wang, Tao Yang, Jing Chen, Zihan Jia, Xueping Li, Xinru Zhang, Shuai Chen, Nannan Cheng, Mengke Zhao, Jiaxin Li, Qidi Xue, Houlian Zhang, Chao Jiang, Na Xing, Kang Ouyang, Albert Pekny, Malgorzata M Michalowska, Yolanda de Pablo, Ulrika Wilhelmsson, Nicholas Mitsios, Chuanyu Liu, Xun Xu, Xiaochong Fan, Marcela Pekna, Milos Pekny, Xuemei Chen, Longqi Liu, Jan Mulder, Mingyue Wang, Jian Wang
{"title":"Spatiotemporal transcriptomic maps of mouse intracerebral hemorrhage at single-cell resolution.","authors":"Rong Xiang, Junmin Wang, Zhan Chen, Jin Tao, Qinfeng Peng, Ruoqi Ding, Tao Zhou, Zhencheng Tu, Shaoshuai Wang, Tao Yang, Jing Chen, Zihan Jia, Xueping Li, Xinru Zhang, Shuai Chen, Nannan Cheng, Mengke Zhao, Jiaxin Li, Qidi Xue, Houlian Zhang, Chao Jiang, Na Xing, Kang Ouyang, Albert Pekny, Malgorzata M Michalowska, Yolanda de Pablo, Ulrika Wilhelmsson, Nicholas Mitsios, Chuanyu Liu, Xun Xu, Xiaochong Fan, Marcela Pekna, Milos Pekny, Xuemei Chen, Longqi Liu, Jan Mulder, Mingyue Wang, Jian Wang","doi":"10.1016/j.neuron.2025.04.026","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.04.026","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH) is a prevalent disease with high mortality. Despite advances in clinical care, the prognosis of ICH remains poor due to an incomplete understanding of the complex pathological processes. To address this challenge, we generated single-cell-resolution spatiotemporal transcriptomic maps of the mouse brain following ICH. This dataset is the most extensive resource available, providing detailed information about the temporal expression of genes along with a high-resolution cellular profile and preserved cellular organization. We identified 100 distinct cell subclasses, 17 of which were found to play significant roles in the pathophysiology of ICH. We also report similarities and differences between two experimental ICH models and human postmortem ICH brain tissue. This study advances the understanding of the local and global responses of brain cells to ICH. It provides a valuable resource that can facilitate future research and aid the development of novel therapies for this devastating condition.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143056","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
TDP-43 seeding induces cytoplasmic aggregation heterogeneity and nuclear loss of function of TDP-43. TDP-43种子诱导细胞质聚集异质性和细胞核功能丧失。
IF 14.7 1区 医学
Neuron Pub Date : 2025-05-21 Epub Date: 2025-03-28 DOI: 10.1016/j.neuron.2025.03.004
Jens Rummens, Bilal Khalil, Günseli Yıldırım, Pedro Silva, Valentina Zorzini, Nicolas Peredo, Marta Wojno, Meine Ramakers, Ludo Van Den Bosch, Philip Van Damme, Kristofer Davie, Jelle Hendrix, Frederic Rousseau, Joost Schymkowitz, Sandrine Da Cruz
{"title":"TDP-43 seeding induces cytoplasmic aggregation heterogeneity and nuclear loss of function of TDP-43.","authors":"Jens Rummens, Bilal Khalil, Günseli Yıldırım, Pedro Silva, Valentina Zorzini, Nicolas Peredo, Marta Wojno, Meine Ramakers, Ludo Van Den Bosch, Philip Van Damme, Kristofer Davie, Jelle Hendrix, Frederic Rousseau, Joost Schymkowitz, Sandrine Da Cruz","doi":"10.1016/j.neuron.2025.03.004","DOIUrl":"10.1016/j.neuron.2025.03.004","url":null,"abstract":"<p><p>Cytoplasmic aggregation and nuclear depletion of TAR DNA-binding protein 43 (TDP-43) are hallmarks of several neurodegenerative disorders. Yet, recapitulating both features in cellular systems has been challenging. Here, we produced amyloid-like fibrils from recombinant TDP-43 low-complexity domain and demonstrate that sonicated fibrils trigger TDP-43 pathology in human cells, including induced pluripotent stem cell (iPSC)-derived neurons. Fibril-induced cytoplasmic TDP-43 inclusions acquire distinct biophysical properties, recapitulate pathological hallmarks such as phosphorylation, ubiquitin, and p62 accumulation, and recruit nuclear endogenous TDP-43, leading to its loss of function. A transcriptomic signature linked to both aggregation and nuclear loss of TDP-43, including disease-specific cryptic splicing, is identified. Cytoplasmic TDP-43 aggregates exhibit time-dependent heterogeneous morphologies as observed in patients-including compacted, filamentous, or fragmented-which involve upregulation/recruitment of protein clearance pathways. Ultimately, cell-specific progressive toxicity is provoked by seeded TDP-43 pathology in human neurons. These findings identify TDP-43-templated aggregation as a key mechanism driving both cytoplasmic gain of function and nuclear loss of function, offering a valuable approach to identify modifiers of sporadic TDP-43 proteinopathies.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"1597-1613.e8"},"PeriodicalIF":14.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743168","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 integrated microfluidic and fluorescence platform for probing in vivo neuropharmacology. 一种用于体内神经药理学探测的集成微流控和荧光平台。
IF 14.7 1区 医学
Neuron Pub Date : 2025-05-21 Epub Date: 2025-04-10 DOI: 10.1016/j.neuron.2025.03.017
Sean C Piantadosi, Min-Kyu Lee, Mingzheng Wu, Huong Huynh, Raudel Avila, Catalina A Zamorano, Carina Pizzano, Yixin Wu, Rachael Xavier, Maria Stanslaski, Jiheon Kang, Sarah Thai, Youngdo Kim, Jinglan Zhang, Yonggang Huang, Yevgenia Kozorovitskiy, Cameron H Good, Anthony R Banks, John A Rogers, Michael R Bruchas
{"title":"An integrated microfluidic and fluorescence platform for probing in vivo neuropharmacology.","authors":"Sean C Piantadosi, Min-Kyu Lee, Mingzheng Wu, Huong Huynh, Raudel Avila, Catalina A Zamorano, Carina Pizzano, Yixin Wu, Rachael Xavier, Maria Stanslaski, Jiheon Kang, Sarah Thai, Youngdo Kim, Jinglan Zhang, Yonggang Huang, Yevgenia Kozorovitskiy, Cameron H Good, Anthony R Banks, John A Rogers, Michael R Bruchas","doi":"10.1016/j.neuron.2025.03.017","DOIUrl":"10.1016/j.neuron.2025.03.017","url":null,"abstract":"<p><p>Neurotechnologies and genetic tools for dissecting neural circuit functions have advanced rapidly over the past decade although the development of complementary pharmacological methodologies has comparatively lagged. Understanding the precise pharmacological mechanisms of neuroactive compounds is critical for advancing basic neurobiology and neuropharmacology, as well as for developing more effective treatments for neurological and neuropsychiatric disorders. However, integrating modern tools for assessing neural activity in large-scale neural networks with spatially localized drug delivery remains a major challenge. Here, we present a dual microfluidic-photometry platform that enables simultaneous intracranial drug delivery with neural dynamics recording in the rodent brain. The integrated platform combines a wireless, battery-free, miniaturized fluidic microsystem with optical probes, allowing for spatially and temporally restricted drug delivery while sensing activity-dependent fluorescence using genetically encoded calcium indicators (GECIs), neurotransmitter sensors, and neuropeptide sensors. We demonstrate the performance of this platform for investigating neuropharmacological mechanisms in vivo in behaving mice.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"1491-1506.e6"},"PeriodicalIF":14.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12097939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015273","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
An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes. 一个增强器- aav工具箱,用于靶向和操纵不同的中间神经元亚型。
IF 14.7 1区 医学
Neuron Pub Date : 2025-05-21 DOI: 10.1016/j.neuron.2025.05.002
Elisabetta Furlanis, Min Dai, Brenda Leyva Garcia, Thien Tran, Josselyn Vergara, Ana Pereira, Bram L Gorissen, Sara Wills, Anna Vlachos, Ariel Hairston, Deepanjali Dwivedi, Sarah Du, Justin McMahon, Shuhan Huang, Annunziato Morabito, Arenski Vazquez, Soyoun Kim, Anthony T Lee, Edward F Chang, Taha Razzaq, Ahmed Qazi, Geoffrey Vargish, Xiaoqing Yuan, Adam Caccavano, Steven Hunt, Ramesh Chittajallu, Nadiya McLean, Lauren Hewitt, Emily Paranzino, Haley Rice, Alex C Cummins, Anya Plotnikova, Arya Mohanty, Anne Claire Tangen, Jung Hoon Shin, Reza Azadi, Mark A G Eldridge, Veronica A Alvarez, Bruno B Averbeck, Mansour Alyahyay, Tania Reyes Vallejo, Mohammed Soheib, Lucas G Vattino, Cathryn P MacGregor, Carolina Piletti Chatain, Emmie Banks, Viktor Janos Olah, Shovan Naskar, Sophie Hill, Sophie Liebergall, Rohan Badiani, Lili Hyde, Ella Hanley, Qing Xu, Kathryn C Allaway, Ethan M Goldberg, Matthew J M Rowan, Tomasz J Nowakowski, Soohyun Lee, Emilia Favuzzi, Pascal S Kaeser, Lucas Sjulson, Renata Batista-Brito, Anne E Takesian, Leena A Ibrahim, Asim Iqbal, Kenneth A Pelkey, Chris J McBain, Jordane Dimidschstein, Gord Fishell, Yating Wang
{"title":"An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes.","authors":"Elisabetta Furlanis, Min Dai, Brenda Leyva Garcia, Thien Tran, Josselyn Vergara, Ana Pereira, Bram L Gorissen, Sara Wills, Anna Vlachos, Ariel Hairston, Deepanjali Dwivedi, Sarah Du, Justin McMahon, Shuhan Huang, Annunziato Morabito, Arenski Vazquez, Soyoun Kim, Anthony T Lee, Edward F Chang, Taha Razzaq, Ahmed Qazi, Geoffrey Vargish, Xiaoqing Yuan, Adam Caccavano, Steven Hunt, Ramesh Chittajallu, Nadiya McLean, Lauren Hewitt, Emily Paranzino, Haley Rice, Alex C Cummins, Anya Plotnikova, Arya Mohanty, Anne Claire Tangen, Jung Hoon Shin, Reza Azadi, Mark A G Eldridge, Veronica A Alvarez, Bruno B Averbeck, Mansour Alyahyay, Tania Reyes Vallejo, Mohammed Soheib, Lucas G Vattino, Cathryn P MacGregor, Carolina Piletti Chatain, Emmie Banks, Viktor Janos Olah, Shovan Naskar, Sophie Hill, Sophie Liebergall, Rohan Badiani, Lili Hyde, Ella Hanley, Qing Xu, Kathryn C Allaway, Ethan M Goldberg, Matthew J M Rowan, Tomasz J Nowakowski, Soohyun Lee, Emilia Favuzzi, Pascal S Kaeser, Lucas Sjulson, Renata Batista-Brito, Anne E Takesian, Leena A Ibrahim, Asim Iqbal, Kenneth A Pelkey, Chris J McBain, Jordane Dimidschstein, Gord Fishell, Yating Wang","doi":"10.1016/j.neuron.2025.05.002","DOIUrl":"10.1016/j.neuron.2025.05.002","url":null,"abstract":"<p><p>In recent years, we and others have identified a number of enhancers that, when incorporated into rAAV vectors, can restrict the transgene expression to particular neuronal populations. Yet, viral tools to access and manipulate specific neuronal subtypes are still limited. Here, we performed systematic analysis of single-cell genomic data to identify enhancer candidates for each of the telencephalic interneuron subtypes. We established a set of enhancer-AAV tools that are highly specific for distinct cortical interneuron populations and striatal cholinergic interneurons. These enhancers, when used in the context of different effectors, can target (fluorescent proteins), observe activity (GCaMP), and manipulate (opto-genetics) specific neuronal subtypes. We also validated our enhancer-AAV tools across species. Thus, we provide the field with a powerful set of tools to study neural circuits and functions and to develop precise and targeted therapy.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":"113 10","pages":"1525-1547.e15"},"PeriodicalIF":14.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128333","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 evolving neurobiology of early-life stress. 早期生活压力的神经生物学进化。
IF 14.7 1区 医学
Neuron Pub Date : 2025-05-21 Epub Date: 2025-03-17 DOI: 10.1016/j.neuron.2025.02.016
Matthew T Birnie, Tallie Z Baram
{"title":"The evolving neurobiology of early-life stress.","authors":"Matthew T Birnie, Tallie Z Baram","doi":"10.1016/j.neuron.2025.02.016","DOIUrl":"10.1016/j.neuron.2025.02.016","url":null,"abstract":"<p><p>Because early-life stress is common and constitutes a strong risk factor for cognitive and mental health disorders, it has been the focus of a multitude of studies in humans and experimental models. Yet, we have an incomplete understanding of what is perceived as stressful by the developing brain, what aspects of stress influence brain maturation, what developmental ages are particularly vulnerable to stress, which molecules mediate the effects of stress on brain operations, and how transient stressful experiences can lead to enduring emotional and cognitive dysfunctions. Here, we discuss these themes, highlight the challenges and progress in resolving them, and propose new concepts and avenues for future research.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"1474-1490"},"PeriodicalIF":14.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12097948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658003","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
Seeded aggregation of TDP-43 induces its loss of function and reveals early pathological signatures. TDP-43的种子聚集诱导其功能丧失并揭示早期病理特征。
IF 14.7 1区 医学
Neuron Pub Date : 2025-05-21 Epub Date: 2025-03-28 DOI: 10.1016/j.neuron.2025.03.008
Carlo Scialò, Weijia Zhong, Somanath Jagannath, Oscar Wilkins, Davide Caredio, Marian Hruska-Plochan, Flavio Lurati, Martina Peter, Elena De Cecco, Luigi Celauro, Adriano Aguzzi, Giuseppe Legname, Pietro Fratta, Magdalini Polymenidou
{"title":"Seeded aggregation of TDP-43 induces its loss of function and reveals early pathological signatures.","authors":"Carlo Scialò, Weijia Zhong, Somanath Jagannath, Oscar Wilkins, Davide Caredio, Marian Hruska-Plochan, Flavio Lurati, Martina Peter, Elena De Cecco, Luigi Celauro, Adriano Aguzzi, Giuseppe Legname, Pietro Fratta, Magdalini Polymenidou","doi":"10.1016/j.neuron.2025.03.008","DOIUrl":"10.1016/j.neuron.2025.03.008","url":null,"abstract":"<p><p>Neurodegeneration in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) results from both gain of toxicity and loss of normal function of the RNA-binding protein TDP-43, but their mechanistic connection remains unclear. Increasing evidence suggests that TDP-43 aggregates act as self-templating seeds, propagating pathology through the central nervous system via a prion-like cascade. We developed a robust TDP-43-seeding platform for quantitative assessment of TDP-43 aggregate uptake, cell-to-cell spreading, and loss of function within living cells, while they progress toward pathology. We show that both patient-derived and recombinant TDP-43 pathological aggregates were abundantly internalized by human neuron-like cells, efficiently recruited endogenous TDP-43, and formed cytoplasmic inclusions reminiscent of ALS/FTD pathology. Combining a fluorescent reporter of TDP-43 function with RNA sequencing and proteomics, we demonstrated aberrant cryptic splicing and a loss-of-function profile resulting from TDP-43-templated aggregation. Our data highlight known and novel pathological signatures in the context of seed-induced TDP-43 loss of function.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"1614-1628.e11"},"PeriodicalIF":14.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743060","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
Exploring brain circuits, one cell type-or more- at a time. 一次探索一种或多种细胞类型的大脑回路。
IF 14.7 1区 医学
Neuron Pub Date : 2025-05-21 DOI: 10.1016/j.neuron.2025.05.001
Bosiljka Tasic, Gord Fishell
{"title":"Exploring brain circuits, one cell type-or more- at a time.","authors":"Bosiljka Tasic, Gord Fishell","doi":"10.1016/j.neuron.2025.05.001","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.05.001","url":null,"abstract":"<p><p>This issue of Neuron, with accompanying papers in Cell, Cell Genomics, Cell Reports, and Cell Reports Methods, contains studies describing methods for access to neuronal and non-neuronal cell types within the central nervous system. Combining technologies including genetics, virology, genomic enhancers, and RNA sensing, these tools enable targeting the nervous system in an unprecedented manner.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":"113 10","pages":"1469-1473"},"PeriodicalIF":14.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128339","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
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