Nature neuroscience最新文献

{"title":"Fructose-induced anxiety","authors":"Laura Zelenka","doi":"10.1038/s41593-025-02019-9","DOIUrl":"10.1038/s41593-025-02019-9","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 7","pages":"1367-1367"},"PeriodicalIF":20.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578399","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":"Enhancers hit their targets","authors":"William P. Olson","doi":"10.1038/s41593-025-02018-w","DOIUrl":"10.1038/s41593-025-02018-w","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 7","pages":"1367-1367"},"PeriodicalIF":20.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578404","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":"Decoding dialogue is a matter of time","authors":"Henrietta Howells","doi":"10.1038/s41593-025-02017-x","DOIUrl":"10.1038/s41593-025-02017-x","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 7","pages":"1367-1367"},"PeriodicalIF":20.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578403","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 thalamocortical structural connectivity develops in line with a hierarchical axis of cortical plasticity","authors":"Valerie J. Sydnor, Joëlle Bagautdinova, Bart Larsen, Michael J. Arcaro, Deanna M. Barch, Dani S. Bassett, Aaron F. Alexander-Bloch, Philip A. Cook, Sydney Covitz, Alexandre R. Franco, Raquel E. Gur, Ruben C. Gur, Allyson P. Mackey, Kahini Mehta, Steven L. Meisler, Michael P. Milham, Tyler M. Moore, Eli J. Müller, David R. Roalf, Taylor Salo, Gabriel Schubiner, Jakob Seidlitz, Russell T. Shinohara, James M. Shine, Fang-Cheng Yeh, Matthew Cieslak, Theodore D. Satterthwaite","doi":"10.1038/s41593-025-01991-6","DOIUrl":"10.1038/s41593-025-01991-6","url":null,"abstract":"Human cortical development follows a hierarchical, sensorimotor-to-association sequence. The brain’s capacity to enact this sequence indicates that it relies on unknown mechanisms to regulate regional differences in the timing of cortical maturation. Given evidence from animal systems that thalamic axons mechanistically regulate periods of cortical plasticity, here we evaluate in humans whether the development of structural connections between the thalamus and cortex aligns with cortical maturational heterochronicity. By deriving a new tractography atlas of human thalamic connections and applying it to diffusion data from three youth samples (8–23 years; total n = 2,676), we demonstrate that thalamocortical connectivity matures in a generalizable manner along the cortex’s sensorimotor–association axis. Associative cortical regions with thalamic connections that take the longest to mature exhibit neurochemical, structural and functional signatures of protracted developmental plasticity as well as heightened sensitivity to the socioeconomic environment. This work highlights the role of the thalamus in the expression of hierarchical periods of cortical developmental plasticity and environmental receptivity. Sydnor et al. developed a new tractography atlas of thalamocortical structural connections and applied it to three youth samples. They uncovered coordinated development between thalamic connectivity and hierarchical cortical plasticity in humans.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 8","pages":"1772-1786"},"PeriodicalIF":20.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564937","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":"Addressing artifactual bias in large, automated MRI analyses of brain development","authors":"Safia Elyounssi, Keiko Kunitoki, Jacqueline A. Clauss, Eline Laurent, Kristina A. Kane, Dylan E. Hughes, Casey E. Hopkinson, Oren Bazer, Rachel Freed Sussman, Alysa E. Doyle, Hang Lee, Brenden Tervo-Clemmens, Hamdi Eryilmaz, Randy L. Hirschtick, Deanna M. Barch, Theodore D. Satterthwaite, Kevin F. Dowling, Joshua L. Roffman","doi":"10.1038/s41593-025-01990-7","DOIUrl":"10.1038/s41593-025-01990-7","url":null,"abstract":"Large, population-based magnetic resonance imaging (MRI) studies of adolescents promise transformational insights into neurodevelopment and mental illness risk. However, youth MRI studies are especially susceptible to motion and other artifacts that introduce non-random noise. After visual quality control of 11,263 T1 MRI scans obtained at age 9–10 years through the Adolescent Brain Cognitive Development study, we uncovered bias in measurements of cortical thickness and surface area in 55.1% of the samples with suboptimal image quality. These biases impacted analyses relating structural MRI and clinical measures, resulting in both false-positive and false-negative associations. Surface hole number, an automated index of topological complexity, reproducibly identified lower-quality scans with good specificity, and its inclusion as a covariate partially mitigated quality-related bias. Closer examination of high-quality scans revealed additional topological errors introduced during image preprocessing. Correction with manual edits reproducibly altered thickness measurements and strengthened age–thickness associations. We demonstrate here that inadequate quality control undermines advantages of large sample size to detect meaningful associations. These biases can be mitigated through additional automated and manual interventions. As large-scale neurodevelopmental MRI studies gain prominence, the authors identify tradeoffs between sample size and quality control that can dramatically affect results, and they evaluate a range of approaches to mitigate risk for error.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 8","pages":"1787-1796"},"PeriodicalIF":20.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520859","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 CLOCK enhances neocortical function","authors":"Yuxiang Liu, Miles R. Fontenot, Ashwinikumar Kulkarni, Nitin Khandelwal, Seon Hye E. Voth Park, Connor Criswell, Matthew Harper, Pin Xu, Nisha Gupta, Jay R. Gibson, Joseph S. Takahashi, Genevieve Konopka","doi":"10.1038/s41593-025-01993-4","DOIUrl":"10.1038/s41593-025-01993-4","url":null,"abstract":"The transcription factor CLOCK is ubiquitously expressed and important for circadian rhythms, while its human-specific expression in neocortex suggests additional functions. Here, we generated a mouse model (HU) that recapitulates human cortical expression of CLOCK. The HU mice show enhanced cognitive flexibility, which might be associated with alteration in spatiotemporal expression of CLOCK. Cell-type-specific genomic profiling identified upregulated genes related to dendritic growth and spine formation in excitatory neurons of HU mice. We also found that excitatory neurons in HU mice have increased dendritic complexity and spine density, and a greater frequency of excitatory postsynaptic currents, suggesting a greater abundance of neural connectivity. In contrast, CLOCK knockout in human induced pluripotent stem cell-derived neurons showed reduced complexity of dendrites and lower density of presynaptic puncta. Together, our data demonstrate that CLOCK might have evolved brain-relevant gains of function via altered spatiotemporal gene expression and that these functions may underlie human brain specializations. Regulation of gene expression is a facet of human brain specialization. Here, the authors show that human-like expression of the CLOCK gene in the mouse neocortex enhances cognitive flexibility and neural connectivity, suggesting an evolutionary gain of function that may have contributed to human cognitive specialization.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 8","pages":"1716-1728"},"PeriodicalIF":20.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515426","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":"Fine-mapping genomic loci refines bipolar disorder risk genes","authors":"Maria Koromina, Ashvin Ravi, Georgia Panagiotaropoulou, Brian M. Schilder, Jack Humphrey, Alice Braun, Tim Bidgeli, Chris Chatzinakos, Brandon J. Coombes, Jaeyoung Kim, Xiaoxi Liu, Chikashi Terao, Kevin S. O’Connell, Mark J. Adams, Rolf Adolfsson, Martin Alda, Lars Alfredsson, Till F. M. Andlauer, Ole A. Andreassen, Anastasia Antoniou, Bernhard T. Baune, Susanne Bengesser, Joanna Biernacka, Michael Boehnke, Rosa Bosch, Murray J. Cairns, Vaughan J. Carr, Miquel Casas, Stanley Catts, Sven Cichon, Aiden Corvin, Nicholas Craddock, Konstantinos Dafnas, Nina Dalkner, Udo Dannlowski, Franziska Degenhardt, Arianna Di Florio, Dimitris Dikeos, Frederike Tabea Fellendorf, Panagiotis Ferentinos, Andreas J. Forstner, Liz Forty, Mark Frye, Janice M. Fullerton, Micha Gawlik, Ian R. Gizer, Katherine Gordon-Smith, Melissa J. Green, Maria Grigoroiu-Serbanescu, José Guzman-Parra, Tim Hahn, Frans Henskens, Jan Hillert, Assen V. Jablensky, Lisa Jones, Ian Jones, Lina Jonsson, John R. Kelsoe, Tilo Kircher, George Kirov, Sarah Kittel-Schneider, Manolis Kogevinas, Mikael Landén, Marion Leboyer, Melanie Lenger, Jolanta Lissowska, Christine Lochner, Carmel Loughland, Donald J. MacIntyre, Nicholas G. Martin, Eirini Maratou, Carol A. Mathews, Fermin Mayoral, Susan L. McElroy, Nathaniel W. McGregor, Andrew McIntosh, Andrew McQuillin, Patricia Michie, Philip B. Mitchell, Paraskevi Moutsatsou, Bryan Mowry, Bertram Müller-Myhsok, Richard M. Myers, Igor Nenadić, Caroline M. Nievergelt, Markus M. Nöthen, John Nurnberger, Michael O. ’Donovan, Claire O. ’Donovan, Roel A. Ophoff, Michael J. Owen, Christos Pantelis, Carlos Pato, Michele T. Pato, George P. Patrinos, Joanna M. Pawlak, Roy H. Perlis, Evgenia Porichi, Danielle Posthuma, Josep Antoni Ramos-Quiroga, Andreas Reif, Eva Z. Reininghaus, Marta Ribasés, Marcella Rietschel, Ulrich Schall, Peter R. Schofield, Thomas G. Schulze, Laura Scott, Rodney J. Scott, Alessandro Serretti, Jordan W. Smoller, Beata Świątkowska, Maria Soler Artigas, Dan J. Stein, Fabian Streit, Claudio Toma, Paul Tooney, Marquis P. Vawter, Eduard Vieta, John B. Vincent, Irwin D. Waldman, Cynthia Shannon Weickert, Thomas Weickert, Stephanie H. Witt, Kyung Sue Hong, Masashi Ikeda, Nakao Iwata, Hong-Hee Won, Howard J. Edenberg, Stephan Ripke, Towfique Raj, Jonathan R. I. Coleman, Niamh Mullins","doi":"10.1038/s41593-025-01998-z","DOIUrl":"10.1038/s41593-025-01998-z","url":null,"abstract":"Bipolar disorder is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 bipolar disorder risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci and prioritized 17 likely causal SNPs for bipolar disorder. We mapped these SNPs to genes and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci and results from rare variant exome sequencing in bipolar disorder. Convergent lines of evidence supported the roles of genes involved in neurotransmission and neurodevelopment, including SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, FKBP2, RASGRP1, FURIN, FES, MED24 and THRA among others in bipolar disorder. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance of bipolar disorder polygenic risk scores across diverse populations and present a high-throughput fine-mapping pipeline. This study used fine-mapping to analyze genetic regions associated with bipolar disorder, identifying specific risk genes and providing new insights into the biology of the condition that may guide future research and treatment approaches.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 7","pages":"1393-1403"},"PeriodicalIF":20.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41593-025-01998-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478967","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":"Large-scale high-density brain-wide neural recording in nonhuman primates","authors":"Eric M. Trautmann, Janis K. Hesse, Gabriel M. Stine, Ruobing Xia, Shude Zhu, Daniel J. O’Shea, Bill Karsh, Jennifer Colonell, Frank F. Lanfranchi, Saurabh Vyas, Andrew Zimnik, Elom Amematsro, Natalie A. Steinemann, Daniel A. Wagenaar, Marius Pachitariu, Alexandru Andrei, Carolina Mora Lopez, John O’Callaghan, Jan Putzeys, Bogdan C. Raducanu, Marleen Welkenhuysen, Mark Churchland, Tirin Moore, Michael Shadlen, Krishna Shenoy, Doris Tsao, Barundeb Dutta, Timothy Harris","doi":"10.1038/s41593-025-01976-5","DOIUrl":"10.1038/s41593-025-01976-5","url":null,"abstract":"High-density silicon probes have transformed neuroscience by enabling large-scale neural recordings at single-cell resolution. However, existing technologies have provided limited functionality in nonhuman primates (NHPs) such as macaques. In the present report, we describe the design, fabrication and performance of Neuropixels 1.0 NHP, a high-channel electrode array designed to enable large-scale acute recording throughout large animal brains. The probe features 4,416 recording sites distributed along a 45-mm shank. Experimenters can programmably select 384 recording channels, enabling simultaneous multi-area recording from thousands of neurons with single or multiple probes. This technology substantially increases scalability and recording access relative to existing technologies and enables new classes of experiments that involve electrophysiological mapping of brain areas at single-neuron and single-spike resolution, measurement of spike–spike correlations between cells and simultaneous brain-wide recordings at scale. Neuropixels 1.0 NHP is a 45-mm, high-density silicon probe capable of recording large numbers of neurons with single-neuron resolution from most areas in a macaque’s brain.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 7","pages":"1562-1575"},"PeriodicalIF":20.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41593-025-01976-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144341178","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":"Closed-loop electrical stimulation prevents focal epilepsy progression and long-term memory impairment","authors":"Jose J. Ferrero, Ahnaf R. Hassan, Zelin Yu, Zifang Zhao, Liang Ma, Cynthia Wu, Shan Shao, Takeshi Kawano, Judah Engel, Werner Doyle, Orrin Devinsky, Dion Khodagholy, Jennifer N. Gelinas","doi":"10.1038/s41593-025-01988-1","DOIUrl":"10.1038/s41593-025-01988-1","url":null,"abstract":"Interictal epileptiform discharges (IEDs) are expressed in epileptic networks and disrupt cognitive functions. It is unclear whether addressing IED-induced dysfunction could improve epilepsy outcomes, as most therapeutic approaches target seizures. We show, in a kindling model of progressive focal epilepsy, that IEDs produce pathological oscillatory coupling associated with prolonged, hypersynchronous neural spiking in synaptically connected cortex and expand the brain territory capable of generating IEDs. A similar relationship between IED-mediated oscillatory coupling and temporal organization of IEDs across brain regions was identified in human participants with refractory focal epilepsy. Spatiotemporally targeted closed-loop electrical stimulation triggered on hippocampal IED occurrence eliminated the abnormal cortical activity patterns, preventing the spread of the epileptic network and ameliorating long-term spatial memory deficits in rodents. These findings suggest that stimulation-based network interventions that normalize interictal dynamics may be an effective treatment of epilepsy and its comorbidities, with a low barrier to clinical translation. Pathological neural communication drives the spread of the epileptic network and contributes to memory impairment in focal epilepsy. The authors show that closed-loop electrical stimulation in rodents can prevent this interaction and preserve long-term memory.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 8","pages":"1753-1762"},"PeriodicalIF":20.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41593-025-01988-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144341290","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":"Heat shock proteins function as signaling molecules to mediate neuron–glia communication in C. elegans during aging","authors":"Jieyu Wu, Victoria R. Yarmey, Olivia Jiaming Yang, Erik J. Soderblom, Adriana San-Miguel, Dong Yan","doi":"10.1038/s41593-025-01989-0","DOIUrl":"10.1038/s41593-025-01989-0","url":null,"abstract":"The nervous system is primarily composed of neurons and glia, and the communication between them has profound roles in regulating the development and function of the brain. Neuron–glia signal transduction is known to be mediated by secreted signals through ligand–receptor interactions on the cell membrane. Here we show a new mechanism for neuron–glia signal transduction, wherein neurons transmit proteins to glia through extracellular vesicles, activating glial signaling pathways. We find that in the amphid sensory organ of Caenorhabditis elegans, different sensory neurons exhibit varying aging rates. This discrepancy in aging is governed by the cross-talk between neurons and glia. We demonstrate that early aged neurons can transmit heat shock proteins to glia via extracellular vesicles. These neuronal heat shock proteins activate the glial IRE1–XBP1 pathway, leading to the transcriptional regulation of chondroitin synthases to protect glia-embedded neurons from aging-associated functional decline. Therefore, our studies unveil a new mechanism for neuron–glia communication in the nervous system and provide new insights into our understanding of brain aging. Glia–neuron interactions are highly complex. Glial cells can sense and modulate different aspects of neuronal activity. Here in Caenorhabditis elegans, the authors show that early aged sensory neurons can transfer proteins via extracellular vesicles to AMsh glia, inducing neuroprotection during aging.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 8","pages":"1635-1648"},"PeriodicalIF":20.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144312249","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}