Neuron最新文献

{"title":"Accelerating biomedical discoveries in brain health through transformative neuropathology of aging and neurodegeneration","authors":"Melissa E. Murray, Colin Smith, Vilas Menon, C. Dirk Keene, Ed Lein, Michael Hawrylycz, Adriano Aguzzi, Brett Benedetti, Katja Brose, Kelsey Caetano-Anolles, Maria Inmaculada Cobos Sillero, John F. Crary, Philip L. De Jager, Arline Faustin, Margaret E. Flanagan, Ozgun Gokce, Seth G.N. Grant, Lea T. Grinberg, David A. Gutman, Elizabeth M.C. Hillman, Zhi Huang, David J. Irwin, David T. Jones, Alifiya Kapasi, Celeste M. Karch, Walter T. Kukull, Tammaryn Lashley, Edward B. Lee, Thomas Lehner, Laura Parkkinen, Maria Pedersen, Dominique Pritchett, Matthew H. Rutledge, Julie A. Schneider, William W. Seeley, Claire E. Shepherd, Tara L. Spires-Jones, Judith A. Steen, Margaret Sutherland, Sanja Vickovic, Bin Zhang, David J. Stewart, Michael J. Keiser, Jacob W. Vogel, Brittany N. Dugger, Hemali Phatnani","doi":"10.1016/j.neuron.2025.06.014","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.06.014","url":null,"abstract":"Transformative neuropathology is redefining human brain research by integrating foundational descriptive pathology with advanced methodologies. These approaches, spanning multi-omics studies and machine learning applications, will drive discovery for the identification of biomarkers, therapeutic targets, and complex disease patterns through comprehensive analyses of postmortem human brain tissue. Yet critical challenges remain, including the sustainability of brain banks, expanding donor participation, strengthening training pipelines, enabling rapid autopsies, supporting collaborative platforms, and integrating data across modalities. Innovations in digital pathology, tissue quality enhancement, harmonization of data standards, and machine learning integration offer opportunities to accelerate tissue-level “pathomics” research in brain health through cross-disciplinary collaborations. Lessons from neuroimaging, particularly in establishing common data frameworks and multi-site collaborations, offer a valuable roadmap for streamlining innovations. In this perspective, we outline actionable solutions for leveraging existing resources and strengthening collaboration -where we envision future opportunities to drive translational discoveries stemming from transformative neuropathology.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":"24 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665140","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":"Neuroanatomical organization of electroacupuncture in modulating gastric function in mice and humans.","authors":"Shun Dong, Lijuan Zhao, Jing Liu, Xuan Sha, Yi Wu, Weili Liu, Junlong Sun, Yangshuai Su, Zhidi Zhuang, Jian Chen, Ying Dong, Beijing Xie, Anqi Zhou, Hongyan Ji, Yuchun Wang, Xiaoman Deng, Xianghong Jing, Qiufu Ma, Nianhong Wang, Shenbin Liu","doi":"10.1016/j.neuron.2025.06.023","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.06.023","url":null,"abstract":"<p><p>Somatosensory-vagal reflexes evoked by electroacupuncture (EA) can modulate visceral functions. However, the underlying principles and neural mechanisms remain poorly understood, hindering further optimization. Here, we identified key neural components essential for EA topographically driving the somatosensory-vagal-gastric reflex in mice. EA drove this reflex via activation of a subset of transient receptor potential vanilloid-1 (TRPV1)⁺ nociceptors marked by the expression of Adra2a and located exclusively in deep fascial tissues. Through TRPV1⁺ fibers, EA activated a subtype of gastro-projecting Oxtr⁺ fibers originating from the dorsal motor nucleus of the vagus (DMV). Genetic ablation of TRPV1⁺ fibers or Oxtr⁺ DMV neurons attenuated EA-induced gastric reflexes. Conversely, optogenetic activation of these neurons was sufficient to drive gastric motility in mice. Using similar stimulation parameters, we demonstrated that EA successfully improved gastric functions in patients with dysmotility-like functional dyspepsia (chictr.org.cn: ChiCTR2300072636). Our findings thus provide a neural anatomical basis for EA topographically to promote and treat gastric motility disorders.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718175","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":"Limited transmission of mixed convergent signals at the mouse retinogeniculate synapse.","authors":"Takuma Sonoda, Qiufen Jiang, Ivan Jara-Marquez, Hannah Radell, Héctor Acarón Ledesma, Wei Wei, Chinfei Chen","doi":"10.1016/j.neuron.2025.06.015","DOIUrl":"10.1016/j.neuron.2025.06.015","url":null,"abstract":"<p><p>There are two broad modes of information transfer in the brain: the labeled line model, where neurons relay inputs they receive, and the mixed tuning model, where neurons transform different inputs. In the visual pathway, information transfer between retinal ganglion cells (RGCs) and dorsal lateral geniculate nucleus (dLGN) neurons is viewed as a labeled line. However, recent work in mice demonstrated that different RGC types, encoding distinct visual features, converge onto a dLGN neuron, raising the question of how the dLGN transforms visual information. Using optogenetics, we activated distinct RGC populations and measured dLGN neuron spiking in vivo. We found that visual response properties of strongly driven dLGN neurons largely match properties of the activated RGC population. While in vitro dual-opsin experiments demonstrate that strong functional convergence from distinct RGC types does occur at modest frequencies, our data largely support a labeled line model of retinogeniculate information transfer in mice.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691070","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":"Epigenome profiling identifies H3K27me3 regulation of extracellular matrix composition in human corticogenesis.","authors":"Nora Ditzer, Ezgi Senoglu, Annika Kolodziejczyk, Theresa M Schütze, Aikaterina Nikolaidi, Karolin Küster, Katrin Sameith, Sevina Dietz, Razvan P Derihaci, Cahit Birdir, Anne Eugster, Mike O Karl, Andreas Dahl, Pauline Wimberger, Franziska Baenke, Claudia Peitzsch, Mareike Albert","doi":"10.1016/j.neuron.2025.06.016","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.06.016","url":null,"abstract":"<p><p>Epigenetic mechanisms regulate gene expression programs during neurogenesis, but the extent of epigenetic remodeling during human cortical development remains unknown. Here, we characterize the epigenetic landscape of the human developing neocortex by leveraging Epi-CyTOF, a mass-cytometry-based approach for the simultaneous single-cell analysis of more than 30 epigenetic marks. We identify Polycomb repressive complex 2 (PRC2)-mediated H3K27me3 as the modification with the strongest cell-type-specific enrichment. Inhibition of PRC2 in human cortical organoids resulted in a shift of neural progenitor cell (NPC) proliferation toward differentiation. Cell-type-specific profiling of H3K27me3 identified neuronal differentiation and extracellular matrix (ECM) genes in the human neocortex. PRC2 inhibition resulted in increased production of the ECM proteins Syndecan 1 and laminin alpha 1. Overall, this study comprehensively characterizes the epigenetic state of specific neural cell types and highlights a novel role for H3K27me3 in regulating the ECM composition in the human developing neocortex.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699048","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":"Forebrain assembloids support the development of fast-spiking human PVALB+ cortical interneurons and uncover schizophrenia-associated defects.","authors":"Ryan M Walsh, Gregg W Crabtree, Kriti Kalpana, Luz Jubierre, So Yeon Koo, Gabriele Ciceri, Joseph A Gogos, Ilya Kruglikov, Lorenz Studer","doi":"10.1016/j.neuron.2025.06.017","DOIUrl":"10.1016/j.neuron.2025.06.017","url":null,"abstract":"<p><p>Disruption of parvalbumin positive (PVALB+) cortical interneurons is implicated in the pathogenesis of schizophrenia. However, how these defects emerge during development remains poorly understood. The protracted, postnatal maturation of PVALB+ cortical interneurons has complicated human pluripotent stem cell (hPSC)-based models for studying their role in neuropsychiatric disease. Here, we present a forebrain assembloid system yielding PVALB+ cortical interneurons that match the molecular identity and distinctive electrophysiology of primary PVALB+ interneurons. We further established a series of isogenic hPSC lines carrying structural variants associated with schizophrenia and identified variant-specific phenotypes affecting cortical interneuron migration, the molecular profile of PVALB+ cortical interneurons, and their ability to regulate cortical network activity, including γ-band oscillations. These findings offer plausible mechanisms for how the disruption of cortical interneuron development may impact schizophrenia risk and provide a human experimental platform to study PVALB+ cortical interneurons in health and disease.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691069","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":"How the brain shifts between external and internal attention.","authors":"Anna C Nobre, Daniela Gresch","doi":"10.1016/j.neuron.2025.06.013","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.06.013","url":null,"abstract":"<p><p>Focusing on relevant contents to guide adaptive behavior is a core property of the brain. For decades, scientists have investigated mechanisms to anticipate, select, prioritize, and prepare sensory signals according to goals, memories, and salient events. More recently, researchers have considered how these attention functions operate within internal representations. However, neither external nor internal attention in isolation captures everyday behavior. The brain frequently and seamlessly shifts between contents from the sensory stream and those held in mind. In this perspective, we ask how the brain shifts between external and internal attention. We describe similarities and differences between selective external and internal attention, present competing hypotheses regarding the operating principles of between-domain shifts, and highlight putative brain areas and mechanisms. We discuss the scarce experimental forays comparing attention shifts between vs. within domains and contemplate how these constrain theoretical and computational models. We conclude by suggesting open questions to guide investigation.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659726","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":"Propagating Motor Cortical Dynamics Facilitate Movement Initiation","authors":"Karthikeyan Balasubramanian, Vasileios Papadourakis, Wei Liang, Kazutaka Takahashi, Matthew D. Best, Aaron J. Suminski, Nicholas G. Hatsopoulos","doi":"10.1016/j.neuron.2025.07.007","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.07.007","url":null,"abstract":"","PeriodicalId":19313,"journal":{"name":"Neuron","volume":"23 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621886","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":"LRRTM2 Functions as a Neurexin Ligand in Promoting Excitatory Synapse Formation","authors":"Jaewon Ko, Marc V. Fuccillo, Robert C. Malenka, Thomas C. Südhof","doi":"10.1016/j.neuron.2025.07.005","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.07.005","url":null,"abstract":"","PeriodicalId":19313,"journal":{"name":"Neuron","volume":"23 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621887","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":"Human stem cell-derived GABAergic interneuron development reveals early emergence of subtype diversity and gradual electrochemical maturation.","authors":"Marina Bershteyn, Hongjun Zhou, Luis Fuentealba, Chun Chen, Geetha Subramanyam, Daniel Cherkowsky, Eric Steven Sevilla, Philip Hampel, Juan Salvatierra, Meliz Sezan, Yves Maury, Steven Havlicek, Sonja Kriks, Seonok Lee, Wai Au, Michael Watson, Olga Kuzmenko, Maria Elena Grimmett, Alexandra Vogel, Fiona Porkka, Yuechen Qiu, Anastasia Nesterova, Derek Anderson, Brianna G Feld, Victoria Hosford, Ji-Hye Jung, Tia Kowal, Alessandro Bulfone, Gautam Banik, Catherine Priest, Jorge J Palop, Cory R Nicholas","doi":"10.1016/j.neuron.2025.06.010","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.06.010","url":null,"abstract":"<p><p>Medial ganglionic eminence-derived inhibitory γ-aminobutyric acid (GABAergic) pallial interneurons (MGE-pINs) are essential regulators of cortical circuits, and their dysfunction is associated with neurological disorders. We developed human MGE-pINs from pluripotent stem cells for the treatment of drug-resistant epilepsy. Here, we analyzed xenografted MGE-pINs from human pluripotent stem cells (hMGE-pINs) over the lifespan of host mice in healthy and epileptic environments using single-nuclei RNA sequencing. Comparative transcriptomics against endogenous human brain datasets revealed that 97% of grafted cells developed into somatostatin (SST) and parvalbumin (PVALB) subtypes, including populations that exhibit selective vulnerability in Alzheimer's disease. Transplanted hMGE-pINs demonstrated rapid emergence of subclass features, progressing through distinct transcriptional states sequentially involving neuronal migration, synapse organization, and membrane maturation. We present molecular, electrophysiological, and morphological data that collectively confirm the derivation of diverse bona fide human SST and PVALB subtypes, providing a high-fidelity model to study hMGE-pIN development as well as a compositional atlas for regenerative cell therapy applications.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619444","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":"Anatomically resolved oscillatory bursts reveal dynamic motifs of thalamocortical activity during naturalistic stimulus viewing.","authors":"Lukas Sebastian Meyerolbersleben, Anton Sirota, Laura Busse","doi":"10.1016/j.neuron.2025.03.030","DOIUrl":"10.1016/j.neuron.2025.03.030","url":null,"abstract":"<p><p>Natural vision requires circuit mechanisms which process complex spatiotemporal stimulus features in parallel. In the mammalian forebrain, one signature of circuit activation is fast oscillatory dynamics, reflected in the local field potential (LFP). Using data from the Allen Neuropixels Visual Coding project, we show that local visual features in naturalistic stimuli induce in mouse primary visual cortex (V1) retinotopically specific oscillations in various frequency bands and V1 layers. Specifically, layer 4 (L4) narrowband gamma was linked to luminance, low-gamma to optic flow, and L4/L5 epsilon oscillations to contrast. These feature-specific oscillations were associated with distinct translaminar spike-phase coupling patterns, which were conserved across a range of stimuli containing the relevant visual features, suggesting that they might constitute feature-specific circuit motifs. Our findings highlight visually induced fast oscillations as markers of dynamic circuit motifs, which may support differential and multiplexed coding of complex visual input and thalamocortical information propagation.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"2196-2214.e6"},"PeriodicalIF":14.7,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003107","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}