Nature neuroscience最新文献

{"title":"Integration across biophysical scales identifies molecular and cellular correlates of person-to-person variability in human brain connectivity","authors":"Bernard Ng, Shinya Tasaki, Kelsey M. Greathouse, Courtney K. Walker, Ada Zhang, Sydney Covitz, Matt Cieslak, Audrey J. Weber, Ashley B. Adamson, Julia P. Andrade, Emily H. Poovey, Kendall A. Curtis, Hamad M. Muhammad, Jakob Seidlitz, Ted Satterthwaite, David A. Bennett, Nicholas T. Seyfried, Jacob Vogel, Chris Gaiteri, Jeremy H. Herskowitz","doi":"10.1038/s41593-024-01788-z","DOIUrl":"10.1038/s41593-024-01788-z","url":null,"abstract":"Brain connectivity arises from interactions across biophysical scales, ranging from molecular to cellular to anatomical to network level. To date, there has been little progress toward integrated analysis across these scales. To bridge this gap, from a unique cohort of 98 individuals, we collected antemortem neuroimaging and genetic data, as well as postmortem dendritic spine morphometric, proteomic and gene expression data from the superior frontal and inferior temporal gyri. Through the integration of the molecular and dendritic spine morphology data, we identified hundreds of proteins that explain interindividual differences in functional connectivity and structural covariation. These proteins are enriched for synaptic structures and functions, energy metabolism and RNA processing. By integrating data at the genetic, molecular, subcellular and tissue levels, we link specific biochemical changes at synapses to connectivity between brain regions. These results demonstrate the feasibility of integrating data from vastly different biophysical scales to provide a more comprehensive understanding of brain connectivity. Integration of postmortem molecular and dendritic spine morphological measurements enables the detection of microscale molecules associated with person-to-person variability in macroscale brain connectivity estimated from antemortem neuroimaging.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 11","pages":"2240-2252"},"PeriodicalIF":21.2,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01788-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555823","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}

{"title":"Ernest Arenas (1962–2024)","authors":"Patrik Ernfors, Gonçalo Castelo-Branco, Per Uhlén, Sten Linnarsson, Ulrika Marklund, Jens Hjerling-Leffler, Onur Dagliyan","doi":"10.1038/s41593-024-01797-y","DOIUrl":"https://doi.org/10.1038/s41593-024-01797-y","url":null,"abstract":"Ernest Arenas, Professor at the Karolinska Institutet, passed away on 15 September 2024 at the age of 62 in Stockholm, Sweden. Ernest made unique contributions to the field of Parkinson’s disease research, with a strong commitment to developing improved treatment strategies through cell replacement therapy.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"10 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519252","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}

{"title":"A trainee-informed model for undergraduate neuroscience research programs serving marginalized students","authors":"Christian Cazares, Maribel Patiño, Minerva Contreras, Julia C. Gorman, Jillybeth Burgado, Sana A. Ali, Quirine van Engen, Eena L. Kosik, Pamela Riviere, Emily T. Baltz, Chimuanya K. Agba, Michael Preston, Akshay Nagarajan, Jianna Cressy, Natalie Paredes, Chiaki Santiago, Kevin L. White","doi":"10.1038/s41593-024-01790-5","DOIUrl":"10.1038/s41593-024-01790-5","url":null,"abstract":"Undergraduate research programs improve career outcomes for historically marginalized students in the US, but low retention rates in postgraduate research persist. As graduate students and postdocs, we present a combination of trainee-informed approaches for tailoring summer research programs to these students’ needs and share key materials to facilitate adoption of these approaches at other institutions.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 11","pages":"2047-2052"},"PeriodicalIF":21.2,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489505","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}

{"title":"Rastermap: a discovery method for neural population recordings","authors":"Carsen Stringer, Lin Zhong, Atika Syeda, Fengtong Du, Maria Kesa, Marius Pachitariu","doi":"10.1038/s41593-024-01783-4","DOIUrl":"https://doi.org/10.1038/s41593-024-01783-4","url":null,"abstract":"<p>Neurophysiology has long progressed through exploratory experiments and chance discoveries. Anecdotes abound of researchers listening to spikes in real time and noticing patterns of activity related to ongoing stimuli or behaviors. With the advent of large-scale recordings, such close observation of data has become difficult. To find patterns in large-scale neural data, we developed ‘Rastermap’, a visualization method that displays neurons as a raster plot after sorting them along a one-dimensional axis based on their activity patterns. We benchmarked Rastermap on realistic simulations and then used it to explore recordings of tens of thousands of neurons from mouse cortex during spontaneous, stimulus-evoked and task-evoked epochs. We also applied Rastermap to whole-brain zebrafish recordings; to wide-field imaging data; to electrophysiological recordings in rat hippocampus, monkey frontal cortex and various cortical and subcortical regions in mice; and to artificial neural networks. Finally, we illustrate high-dimensional scenarios where Rastermap and similar algorithms cannot be used effectively.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"6 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439690","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}

{"title":"Integrating brainstem and cortical functional architectures","authors":"Justine Y. Hansen, Simone Cauzzo, Kavita Singh, María Guadalupe García-Gomar, James M. Shine, Marta Bianciardi, Bratislav Misic","doi":"10.1038/s41593-024-01787-0","DOIUrl":"https://doi.org/10.1038/s41593-024-01787-0","url":null,"abstract":"<p>The brainstem is a fundamental component of the central nervous system, yet it is typically excluded from in vivo human brain mapping efforts, precluding a complete understanding of how the brainstem influences cortical function. In this study, we used high-resolution 7-Tesla functional magnetic resonance imaging to derive a functional connectome encompassing cortex and 58 brainstem nuclei spanning the midbrain, pons and medulla. We identified a compact set of integrative hubs in the brainstem with widespread connectivity with cerebral cortex. Patterns of connectivity between brainstem and cerebral cortex manifest as neurophysiological oscillatory rhythms, patterns of cognitive functional specialization and the unimodal–transmodal functional hierarchy. This persistent alignment between cortical functional topographies and brainstem nuclei is shaped by the spatial arrangement of multiple neurotransmitter receptors and transporters. We replicated all findings using 3-Tesla data from the same participants. Collectively, this work demonstrates that multiple organizational features of cortical activity can be traced back to the brainstem.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439688","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}

{"title":"The hippocampal CA2 region discriminates social threat from social safety","authors":"Pegah Kassraian,&nbsp;Shivani K. Bigler,&nbsp;Diana M. Gilly Suarez,&nbsp;Neilesh Shrotri,&nbsp;Anastasia Barnett,&nbsp;Heon-Jin Lee,&nbsp;W. Scott Young,&nbsp;Steven A. Siegelbaum","doi":"10.1038/s41593-024-01771-8","DOIUrl":"10.1038/s41593-024-01771-8","url":null,"abstract":"The dorsal cornu ammonis 2 (dCA2) region of the hippocampus enables the discrimination of novel from familiar conspecifics. However, the neural bases for more complex social–spatial episodic memories are unknown. Here we report that the spatial and social contents of an aversive social experience require distinct hippocampal regions. While dorsal CA1 (dCA1) pyramidal neurons mediate the memory of an aversive location, dCA2 pyramidal neurons enable the discrimination of threat-associated (CS+) from safety-associated (CS−) conspecifics in both female and male mice. Silencing dCA2 during encoding or recall trials disrupted social fear discrimination memory, resulting in fear responses toward both the CS+ and CS− mice. Calcium imaging revealed that the aversive experience strengthened and stabilized dCA2 representations of both the CS+ and CS− mice, with the incorporation of an abstract representation of social valence into representations of social identity. Thus, dCA2 contributes to both social novelty detection and the adaptive discrimination of threat-associated from safety-associated individuals during an aversive social episodic experience. The hippocampal dorsal CA2 enables the recognition of novel conspecifics. Kassraian et al. show that it is also required for discriminating safety- versus threat-associated conspecifics and that its disruption gives rise to generalized social avoidance.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 11","pages":"2193-2206"},"PeriodicalIF":21.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436324","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}

{"title":"A cross-disease resource of living human microglia identifies disease-enriched subsets and tool compounds recapitulating microglial states","authors":"John F. Tuddenham, Mariko Taga, Verena Haage, Victoria S. Marshe, Tina Roostaei, Charles White, Annie J. Lee, Masashi Fujita, Anthony Khairallah, Ya Zhang, Gilad Green, Bradley Hyman, Matthew Frosch, Sarah Hopp, Thomas G. Beach, Geidy E. Serrano, John Corboy, Naomi Habib, Hans-Ulrich Klein, Rajesh Kumar Soni, Andrew F. Teich, Richard A. Hickman, Roy N. Alcalay, Neil Shneider, Julie Schneider, Peter A. Sims, David A. Bennett, Marta Olah, Vilas Menon, Philip L. De Jager","doi":"10.1038/s41593-024-01764-7","DOIUrl":"https://doi.org/10.1038/s41593-024-01764-7","url":null,"abstract":"<p>Human microglia play a pivotal role in neurological diseases, but we still have an incomplete understanding of microglial heterogeneity, which limits the development of targeted therapies directly modulating their state or function. Here, we use single-cell RNA sequencing to profile 215,680 live human microglia from 74 donors across diverse neurological diseases and CNS regions. We observe a central divide between oxidative and heterocyclic metabolism and identify microglial subsets associated with antigen presentation, motility and proliferation. Specific subsets are enriched in susceptibility genes for neurodegenerative diseases or the disease-associated microglial signature. We validate subtypes in situ with an RNAscope–immunofluorescence pipeline and high-dimensional MERFISH. We also leverage our dataset as a classification resource, finding that induced pluripotent stem cell model systems capture substantial in vivo heterogeneity. Finally, we identify and validate compounds that recapitulate certain subtypes in vitro, including camptothecin, which downregulates the signature of disease-enriched subtypes and upregulates a signature previously associated with Alzheimer’s disease.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"17 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436339","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}

{"title":"Integrated multimodal cell atlas of Alzheimer’s disease","authors":"Mariano I. Gabitto, Kyle J. Travaglini, Victoria M. Rachleff, Eitan S. Kaplan, Brian Long, Jeanelle Ariza, Yi Ding, Joseph T. Mahoney, Nick Dee, Jeff Goldy, Erica J. Melief, Anamika Agrawal, Omar Kana, Xingjian Zhen, Samuel T. Barlow, Krissy Brouner, Jazmin Campos, John Campos, Ambrose J. Carr, Tamara Casper, Rushil Chakrabarty, Michael Clark, Jonah Cool, Rachel Dalley, Martin Darvas, Song-Lin Ding, Tim Dolbeare, Tom Egdorf, Luke Esposito, Rebecca Ferrer, Lynn E. Fleckenstein, Rohan Gala, Amanda Gary, Emily Gelfand, Jessica Gloe, Nathan Guilford, Junitta Guzman, Daniel Hirschstein, Windy Ho, Madison Hupp, Tim Jarsky, Nelson Johansen, Brian E. Kalmbach, Lisa M. Keene, Sarah Khawand, Mitchell D. Kilgore, Amanda Kirkland, Michael Kunst, Brian R. Lee, Mckaila Leytze, Christine L. Mac Donald, Jocelin Malone, Zoe Maltzer, Naomi Martin, Rachel McCue, Delissa McMillen, Gonzalo Mena, Emma Meyerdierks, Kelly P. Meyers, Tyler Mollenkopf, Mark Montine, Amber L. Nolan, Julie K. Nyhus, Paul A. Olsen, Maiya Pacleb, Chelsea M. Pagan, Nicholas Peña, Trangthanh Pham, Christina Alice Pom, Nadia Postupna, Christine Rimorin, Augustin Ruiz, Giuseppe A. Saldi, Aimee M. Schantz, Nadiya V. Shapovalova, Staci A. Sorensen, Brian Staats, Matt Sullivan, Susan M. Sunkin, Carol Thompson, Michael Tieu, Jonathan T. Ting, Amy Torkelson, Tracy Tran, Nasmil J. Valera Cuevas, Sarah Walling-Bell, Ming-Qiang Wang, Jack Waters, Angela M. Wilson, Ming Xiao, David Haynor, Nicole M. Gatto, Suman Jayadev, Shoaib Mufti, Lydia Ng, Shubhabrata Mukherjee, Paul K. Crane, Caitlin S. Latimer, Boaz P. Levi, Kimberly A. Smith, Jennie L. Close, Jeremy A. Miller, Rebecca D. Hodge, Eric B. Larson, Thomas J. Grabowski, Michael Hawrylycz, C. Dirk Keene, Ed S. Lein","doi":"10.1038/s41593-024-01774-5","DOIUrl":"https://doi.org/10.1038/s41593-024-01774-5","url":null,"abstract":"<p>Alzheimer’s disease (AD) is the leading cause of dementia in older adults. Although AD progression is characterized by stereotyped accumulation of proteinopathies, the affected cellular populations remain understudied. Here we use multiomics, spatial genomics and reference atlases from the BRAIN Initiative to study middle temporal gyrus cell types in 84 donors with varying AD pathologies. This cohort includes 33 male donors and 51 female donors, with an average age at time of death of 88 years. We used quantitative neuropathology to place donors along a disease pseudoprogression score. Pseudoprogression analysis revealed two disease phases: an early phase with a slow increase in pathology, presence of inflammatory microglia, reactive astrocytes, loss of somatostatin⁺ inhibitory neurons, and a remyelination response by oligodendrocyte precursor cells; and a later phase with exponential increase in pathology, loss of excitatory neurons and Pvalb⁺ and Vip⁺ inhibitory neuron subtypes. These findings were replicated in other major AD studies.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"13 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431134","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}

{"title":"Modeling Parkinson’s disease pathology in human dopaminergic neurons by sequential exposure to α-synuclein fibrils and proinflammatory cytokines","authors":"Armin Bayati, Riham Ayoubi, Adriana Aguila, Cornelia E. Zorca, Ghislaine Deyab, Chanshuai Han, Sherilyn Junelle Recinto, Emmanuelle Nguyen-Renou, Cecilia Rocha, Gilles Maussion, Wen Luo, Irina Shlaifer, Emily Banks, Ian McDowell, Esther Del Cid Pellitero, Xue Er Ding, Behrang Sharif, Philippe Séguéla, Moein Yaqubi, Carol X.-Q. Chen, Zhipeng You, Narges Abdian, Heidi M. McBride, Edward A. Fon, Jo Anne Stratton, Thomas M. Durcan, Patrick C. Nahirney, Peter S. McPherson","doi":"10.1038/s41593-024-01775-4","DOIUrl":"https://doi.org/10.1038/s41593-024-01775-4","url":null,"abstract":"<p>Lewy bodies (LBs), α-synuclein-enriched intracellular inclusions, are a hallmark of Parkinson’s disease (PD) pathology, yet a cellular model for LB formation remains elusive. Recent evidence indicates that immune dysfunction may contribute to the development of PD. In this study, we found that induced pluripotent stem cell (iPSC)-derived human dopaminergic (DA) neurons form LB-like inclusions after treatment with α-synuclein preformed fibrils (PFFs) but only when coupled to a model of immune challenge (interferon-γ or interleukin-1β treatment) or when co-cultured with activated microglia-like cells. Exposure to interferon-γ impairs lysosome function in DA neurons, contributing to LB formation. The knockdown of LAMP2 or the knockout of GBA in conjunction with PFF administration is sufficient for inclusion formation. Finally, we observed that the LB-like inclusions in iPSC-derived DA neurons are membrane bound, suggesting that they are not limited to the cytoplasmic compartment but may be formed due to dysfunctions in autophagy. Together, these data indicate that immune-triggered lysosomal dysfunction may contribute to the development of PD pathology.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"70 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384424","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}

{"title":"Perturbing the line","authors":"Luis A. Mejia","doi":"10.1038/s41593-024-01779-0","DOIUrl":"10.1038/s41593-024-01779-0","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 10","pages":"1861-1861"},"PeriodicalIF":21.2,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374553","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}