NeuronPub Date : 2025-10-01DOI: 10.1016/j.neuron.2025.09.016
Lynn van Olst, David Gate
{"title":"Unraveling neurovascular disease risk with MultiVINE-seq.","authors":"Lynn van Olst, David Gate","doi":"10.1016/j.neuron.2025.09.016","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.09.016","url":null,"abstract":"<p><p>In this issue of Neuron, Reid et al. introduce MultiVINE-seq, a single-nucleus multi-omic platform for profiling human cerebrovascular and perivascular cells for paired transcriptomic and epigenomic profiling.<sup>1</sup> By integrating genome-wide association data, they map neurodegenerative and cerebrovascular disease risk variants to specific vascular and immune cell types, uncovering distinct and convergent pathogenic pathways.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":"113 19","pages":"3065-3067"},"PeriodicalIF":15.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213304","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}
NeuronPub Date : 2025-10-01Epub Date: 2025-07-11DOI: 10.1016/j.neuron.2025.06.010
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
{"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":"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":"3162-3184.e10"},"PeriodicalIF":15.0,"publicationDate":"2025-10-01","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":"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":"3260-3274.e5"},"PeriodicalIF":15.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12422097/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeuronPub Date : 2025-10-01DOI: 10.1016/j.neuron.2025.08.027
Luis Ulloa, Yong-Qing Yang
{"title":"Decoding acupuncture somatotopic maps for neuromodulation.","authors":"Luis Ulloa, Yong-Qing Yang","doi":"10.1016/j.neuron.2025.08.027","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.08.027","url":null,"abstract":"<p><p>In this issue of Neuron, Dong et al.<sup>1</sup> describe neural pathways involved in electroacupuncture (EA) stimulation of gastric motility in mice. Their findings improve treatments for functional dyspepsia patients. Recent breakthroughs in the field enable emerging bioelectronic neuromodulation therapies for gastrointestinal disorders.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":"113 19","pages":"3072-3075"},"PeriodicalIF":15.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213247","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}
NeuronPub Date : 2025-10-01Epub Date: 2025-07-21DOI: 10.1016/j.neuron.2025.06.017
Ryan M Walsh, Gregg W Crabtree, Kriti Kalpana, Luz Jubierre, So Yeon Koo, Gabriele Ciceri, Joseph A Gogos, Ilya Kruglikov, Lorenz Studer
{"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":"3185-3203.e7"},"PeriodicalIF":15.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447774/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dissecting human cortical similarity networks across the lifespan.","authors":"Xinyuan Liang, Lianglong Sun, Mingrui Xia, Tengda Zhao, Gaolang Gong, Qiongling Li, Xuhong Liao, Zaixu Cui, Dingna Duan, Chenxuan Pang, Qian Wang, Qian Yu, Yanchao Bi, Pindong Chen, Rui Chen, Yuan Chen, Taolin Chen, Jingliang Cheng, Yuqi Cheng, Zhengjia Dai, Yao Deng, Yuyin Ding, Qi Dong, Jia-Hong Gao, Qiyong Gong, Ying Han, Zaizhu Han, Chu-Chung Huang, Ruiwang Huang, Ran Huo, Lingjiang Li, Ching-Po Lin, Qixiang Lin, Bangshan Liu, Chao Liu, Ningyu Liu, Ying Liu, Yong Liu, Jing Lu, Leilei Ma, Weiwei Men, Shaozheng Qin, Wen Qin, Jiang Qiu, Shijun Qiu, Tianmei Si, Shuping Tan, Yanqing Tang, Sha Tao, Dawei Wang, Fei Wang, Jiali Wang, Jinhui Wang, Pan Wang, Xiaoqin Wang, Yanpei Wang, Dongtao Wei, Yankun Wu, Peng Xie, Xiufeng Xu, Yuehua Xu, Zhilei Xu, Liyuan Yang, Chunshui Yu, Huishu Yuan, Zilong Zeng, Haibo Zhang, Xi Zhang, Gai Zhao, Yanting Zheng, Suyu Zhong, Yong He","doi":"10.1016/j.neuron.2025.06.018","DOIUrl":"10.1016/j.neuron.2025.06.018","url":null,"abstract":"<p><p>The human cortex exhibits remarkable morphometric similarity between regions; however, the form and extent of lifespan network remodeling remain unknown. Here, we show the spatiotemporal maturation of morphometric brain networks, using multimodal neuroimaging data from 33,937 healthy participants aged 0-80 years. Global architecture matures from birth to early adulthood through enhanced modularity and small worldness. Early development features cytoarchitecturally distinct remodeling: sensory cortices exhibit increased morphometric differentiation, paralimbic cortices show increased morphometric similarity, and association cortices retain stable hub roles. Morphology-function coupling peaks in early adolescence and then decreases, supporting protracted functional maturation. These growth patterns of morphometric networks are correlated with gene expression related to synaptic signaling, neurodevelopment, and metabolism. Normative models based on morphometric networks identify person-specific, connectivity-phenotypic deviations in 1,202 patients with brain disorders. These data provide a blueprint for elucidating the principle of cortical network reconfiguration and a benchmark for quantifying interindividual network variations.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"3275-3295.e11"},"PeriodicalIF":15.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708319","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}
NeuronPub Date : 2025-10-01Epub Date: 2025-06-16DOI: 10.1016/j.neuron.2025.05.025
Yiming Shi, Jiaxi Hu, Tian Xue
{"title":"Light, opsins, and life: Mammalian photophysiological functions beyond image perception.","authors":"Yiming Shi, Jiaxi Hu, Tian Xue","doi":"10.1016/j.neuron.2025.05.025","DOIUrl":"10.1016/j.neuron.2025.05.025","url":null,"abstract":"<p><p>Light, a fundamental form of energy and sensory input, has significantly shaped life forms on Earth. In mammals, light perception through the eyes, which enables image formation, is crucial for survival. However, beyond image-forming (IF) vision, light also mediates non-image-forming (NIF) functions, such as circadian photoentrainment and the pupillary light reflex. Recent studies have further demonstrated that light influences a wide range of physiological and behavioral processes, including mood, metabolism, cognition, pain perception, sleep, and neuronal development. The diverse types of opsins, the major photosensitive proteins in mammals, are expressed not only in the rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) of the retina but also in extraocular tissues, such as the brain, skin, and adipose tissue. Opsins in both ocular and extraocular tissues jointly contribute to light detection and mediate diverse NIF functions. In this review, we focus on the NIF effects of light on mammals, emphasizing its regulation of physiological functions as well as the corresponding roles of light receptors and associated neuronal circuits. It also highlights the implications of these findings for human health, underscoring the need for a comprehensive understanding of the interactions between light and life.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"3108-3128"},"PeriodicalIF":15.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317533","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}
NeuronPub Date : 2025-10-01Epub Date: 2025-07-28DOI: 10.1016/j.neuron.2025.07.001
Madigan M Reid, Shreya Menon, Hao Liu, Haoyue Zhou, Zhirui Hu, Simon Frerich, Bella Ding, Shahram Oveisgharan, Zimo Zhang, Sophia Nelson, Amanda Apolonio, David A Bennett, Martin Dichgans, Katherine S Pollard, M Ryan Corces, Andrew C Yang
{"title":"Human brain vascular multi-omics elucidates disease-risk associations.","authors":"Madigan M Reid, Shreya Menon, Hao Liu, Haoyue Zhou, Zhirui Hu, Simon Frerich, Bella Ding, Shahram Oveisgharan, Zimo Zhang, Sophia Nelson, Amanda Apolonio, David A Bennett, Martin Dichgans, Katherine S Pollard, M Ryan Corces, Andrew C Yang","doi":"10.1016/j.neuron.2025.07.001","DOIUrl":"10.1016/j.neuron.2025.07.001","url":null,"abstract":"<p><p>Cerebrovascular dysfunction underlies many neurological disorders, yet how genetic variants in brain vascular cells drive disease risk remains unknown. We developed MultiVINE-seq to simultaneously profile RNA and chromatin accessibility in vascular, perivascular, and immune cells from 30 human brains. Mapping genome-wide association study (GWAS) data to our multi-omic atlas linked thousands of GWAS disease-risk variants to target cell types and genes, including 2,605 previously unmapped. We found cerebrovascular and neurodegenerative disease variants have distinct mechanisms: cerebrovascular disease variants disrupt extracellular matrix genes in endothelial, mural, and fibroblast cells important for vessel structural integrity, while Alzheimer's disease (AD) variants dysregulate inflammatory adaptor proteins in endothelial and immune cells. Notably, a lead AD variant enhances PTK2B expression in brain CD8 T cells, providing genetic evidence for adaptive immunity in AD pathogenesis. This work provides a key resource for interpreting genetic risk and reveals how variants in vascular cells drive divergent pathogenic mechanisms across neurological diseases.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"3143-3161.e5"},"PeriodicalIF":15.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144743339","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}
NeuronPub Date : 2025-10-01Epub Date: 2025-09-18DOI: 10.1016/j.neuron.2025.08.009
Baljit S Khakh
{"title":"On astrocyte-neuron interactions: Broad insights from the striatum.","authors":"Baljit S Khakh","doi":"10.1016/j.neuron.2025.08.009","DOIUrl":"10.1016/j.neuron.2025.08.009","url":null,"abstract":"<p><p>A long-standing question in biology and medicine concerns how astrocytes influence neurons. Here, progress concerning how astrocytes affect neurons and neural circuits is summarized by focusing on data and concepts from studies of the striatum, which has emerged as a model nucleus. Mechanisms broadly applicable across brain regions and disorders are emphasized, and knowledge gaps are described. Experiments spanning multiple scales of biology show that astrocytes regulate neural circuits by virtue of homeostatic signaling and through astrocyte-neuron interactions. During disease, astrocytes contribute to nervous system malfunction in context-specific ways through failures of normal functions and the development of maladaptive responses. As ideally positioned endogenous cellular neuromodulators, astrocytes can be targeted for strategies to regulate neural circuits in brain disorders. After a historically slow start for the field, astrocyte-neuron interactions are now recognized as consequential for physiology and behavior, critically involved in pathophysiology, and exploitable in disease.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"3079-3107"},"PeriodicalIF":15.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092173","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}
NeuronPub Date : 2025-10-01DOI: 10.1016/j.neuron.2025.09.003
Kia M Barclay, Qingyun Li
{"title":"Microglial ADGRG1: AD glial resilience generator.","authors":"Kia M Barclay, Qingyun Li","doi":"10.1016/j.neuron.2025.09.003","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.09.003","url":null,"abstract":"<p><p>Microglial states underlying Alzheimer's disease (AD) have been well characterized in animal models and human samples, yet their regulation remains elusive. In this issue of Neuron, Zhu et al.<sup>1</sup> uncover Adgrg1, which governs a protective microglia phenotype through MYC activation.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":"113 19","pages":"3070-3072"},"PeriodicalIF":15.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213346","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}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
