eLife最新文献

{"title":"Wnt induces FZD5/8 endocytosis and degradation and the involvement of RSPO-ZNRF3/RNF43 and DVL.","authors":"Dong Luo, Jing Zheng, Shuning Lv, Ren Sheng, Maorong Chen, Xi He, Xinjun Zhang","doi":"10.7554/eLife.103996","DOIUrl":"https://doi.org/10.7554/eLife.103996","url":null,"abstract":"<p><p>Frizzled (FZD) proteins are the principal receptors of the Wnt signaling pathway. However, whether Wnt ligands induce FZD endocytosis and degradation remains elusive. The transmembrane E3 ubiquitin ligases ZNRF3 and RNF43 promote the endocytosis and degradation of FZD receptors to inhibit Wnt signaling, and their function is antagonized by R-spondin (RSPO) proteins. However, the dependency of RSPO-ZNRF3/RNF43-mediated FZD endocytosis and degradation on Wnt stimulation, as well as the specificity of this degradation for different FZD, remains unclear. Here, we demonstrated that Wnt specifically induces FZD5/8 endocytosis and degradation in a ZNRF3/RNF43-dependent manner. ZNRF3/RNF43 selectively targets FZD5/8 for degradation upon Wnt stimulation. RSPO1 enhances Wnt signaling by specifically stabilizing FZD5/8. Wnt promotes the interaction between FZD5 and RNF43. We further demonstrated that DVL proteins promote ligand-independent endocytosis of FZD but are dispensable for Wnt-induced FZD5/8 endocytosis and degradation. Our results reveal a novel negative regulatory mechanism of Wnt signaling at the receptor level and illuminate the mechanism by which RSPO-ZNRF3/RNF43 regulates Wnt signaling in human cells, which may provide new insights into regenerative medicine and cancer therapy.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12513720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Forecasting the spatial spread of an Ebola epidemic in real time: Comparing predictions of mathematical models and experts.","authors":"James D Munday, Alicia Rosello, John Edmunds, Sebastian Funk","doi":"10.7554/eLife.98005","DOIUrl":"https://doi.org/10.7554/eLife.98005","url":null,"abstract":"<p><strong>Background: </strong>Ebola virus disease outbreaks can often be controlled, but require rapid response efforts frequently with profound operational complexities. Mathematical models can be used to support response planning, but it is unclear if models improve the prior understanding of experts.</p><p><strong>Methods: </strong>We performed repeated surveys of Ebola response experts during an outbreak. From each expert, we elicited the probability of cases exceeding four thresholds between 2 and 20 cases in a set of small geographical areas in the following calendar month. We compared the predictive performance of these forecasts to those of two mathematical models with different spatial interaction components.</p><p><strong>Results: </strong>An ensemble combining the forecasts of all experts performed similarly to the two models. Experts showed stronger bias than models forecasting two-case threshold exceedance. Experts and models both performed better when predicting exceedance of higher thresholds. The models also tended to be better at risk-ranking areas than experts.</p><p><strong>Conclusions: </strong>Our results support the use of models in outbreak contexts, offering a convenient and scalable route to a quantified situational awareness, which can provide confidence in or to call into question existing advice of experts. There could be value in combining expert opinion and modelled forecasts to support the response to future outbreaks.</p><p><strong>Funding: </strong>This study was partly funded by the Department of Health and Social Care using UK Aid funding 47 and is managed by the National Institute for Health and Care Research (VEEPED: PR-OD-1017- 48 20002; AR and WJE). This study was partly funded by the Wellcome Trust (210758/Z/18/Z : JDM 49 and SF). The views expressed in this publication are those of the authors and not necessarily 50 those of the funders.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12513718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic regulation of immune memory and function of microglia.","authors":"Nikolaos Nirakis, Sofia Dimothyra, Eleftheria Karadima, Vasileia Ismini Alexaki","doi":"10.7554/eLife.107552","DOIUrl":"https://doi.org/10.7554/eLife.107552","url":null,"abstract":"<p><p>Innate immune cells possess memory-like properties. Exposure to infections or sterile inflammation can prime them, leading to either exacerbated inflammatory responses, a process called trained immunity, or reduced responsiveness to pro-inflammatory signals, a process termed immune tolerance. Microglia, the resident innate immune cells of the central nervous system, are central players in neurodegenerative diseases. Characterizing trained immunity and tolerance in microglia is necessary for a better understanding of neurodegenerative diseases. Cell metabolic processes orchestrate microglia inflammatory responses and promote epigenetic changes shaping immune memory in microglia. Here, we review current knowledge on the role of cell metabolic pathways in microglia innate immune memory formation, focusing on glucose, glutamine, and lipid metabolism. Moreover, we address the significance of microglial immune memory in disease pathology and discuss the potential of therapeutic targeting of cell metabolic pathways in neurodegenerative disorders.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12513719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer-immune coevolution dictated by antigenic mutation accumulation.","authors":"Long Wang, Christo Morison, Weini Huang","doi":"10.7554/eLife.103970","DOIUrl":"https://doi.org/10.7554/eLife.103970","url":null,"abstract":"<p><p>The immune system is one of the first lines of defence against cancer. When effector cells attempt to suppress tumour, cancer cells can evolve methods of escape or inhibition. Knowledge of this coevolutionary system can help to understand tumour-immune dynamics both during tumourigenesis and during immunotherapy treatments. Here, we present an individual-based model of mutation accumulation, where random mutations in cancer cells trigger specialised immune responses. Unlike previous research, we explicitly model interactions between cancer and effector cells and incorporate stochastic effects, which are important for the expansion and extinction of small populations. We find that the parameters governing interactions between the cancer and effector cells induce different outcomes of tumour progress, such as suppression and evasion. While it is hard to measure the cancer-immune dynamics directly, genetic information of the cancer may indicate the presence of such interactions. Our model demonstrates signatures of selection in sequencing-derived summary statistics, such as the single-cell mutational burden distribution. Thus, bulk and single-cell sequencing may provide information about the coevolutionary dynamics.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12513721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic stress impairs autoinhibition in neurons of the locus coeruleus to increase asparagine endopeptidase activity.","authors":"Hiroki Toyoda, Doyun Kim, Byeong Geon Koh, Tomomi Sano, Takashi Kanematsu, Seog Bae Oh, Youngnam Kang","doi":"10.7554/eLife.106362","DOIUrl":"10.7554/eLife.106362","url":null,"abstract":"<p><p>Impairments of locus coeruleus (LC) are implicated in anxiety/depression and Alzheimer's disease (AD). Increases in cytosolic noradrenaline (NA) concentration and monoamine oxidase A (MAO-A) activity initiate the LC impairment through production of NA metabolite, 3,4-dihydroxyphenyl-glycolaldehyde (DOPEGAL), by MAO-A. However, how NA accumulates in soma/dendritic cytosol of LC neurons has never been addressed despite the fact that NA is virtually absent in cytosol while NA is produced exclusively in cytoplasmic vesicles from dopamine by dopamine-β-hydroxylase. Since reuptake of autocrine-released NA following spike activity is the major source of NA accumulation, we investigated whether and how chronic stress can increase the spike activity accompanied by NA autocrine. Overexcitation of LC neurons is normally prevented by the autoinhibition mediated by activation of α2A-adrenergic receptor (AR)-coupled inwardly rectifying potassium-current (GIRK-I) with autocrine-released NA. Patch-clamp study revealed that NA-induced GIRK-I in LC neurons was decreased in chronic restraint stress (RS) mice, while a similar decrease was gradually caused by repeated excitation. Chronic RS caused internalization of α2A-ARs expressed in cell membrane in LC neurons and decreased protein/mRNA levels of α2A-ARs/GIRKs in membrane fraction. Subsequently, chronic RS increased the protein levels of MAO-A, DOPEGAL-induced asparagine endopeptidase (AEP), and tau N368. These results suggest that chronic RS-induced overexcitation due to the internalization of α2A-ARs/GIRK is accompanied by [Ca²⁺]_i increases, subsequently increasing Ca²⁺-dependent MAO-A activity and NA autocrine. Thus, it is likely that internalization of α2A-AR increased cytosolic NA, as reflected in AEP increases, by facilitating reuptake of autocrine-released NA. The suppression of α2A-AR internalization may have a translational potential for anxiety/AD treatment.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12510684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Desmodium</i> volatiles in 'push-pull' cropping systems and protection against the fall armyworm, <i>Spodoptera frugiperda</i>.","authors":"Daria M Odermatt, Frank Chidawanyika, Daniel M Mutyambai, Bernhard Schmid, Luiz A Domeignoz Horta, Collins O Onjura, Amanuel Tamiru, Meredith C Schuman","doi":"10.7554/eLife.100981","DOIUrl":"10.7554/eLife.100981","url":null,"abstract":"<p><p>Push-pull systems for sustainable pest management combine repellent stimuli from intercrops ('push') and attractive stimuli from border plants ('pull') to repel herbivorous insects from a main crop and attract the herbivores' natural enemies. The most widespread implementation, intercropping the legume <i>Desmodium</i> with maize surrounded by border grass, reduces damage from the invasive fall armyworm (FAW) <i>Spodoptera frugiperda</i>. While initial research indicated that <i>Desmodium</i> volatiles can dampen the attraction of FAW to maize, a recent study recovered very low volatile emission from the commonly used <i>D. intortum</i> and found that the <i>D. intortum</i> headspace did not reduce FAW oviposition on maize (Erdei et al., 2024). Here, we detect volatiles from the headspace of two <i>Desmodium</i> species sampled within the activity window of FAW: <i>D. intortum</i> and the more recently adopted <i>D. incanum</i>; and we present the behavior of gravid FAW moths in bioassays. We detected 25 volatiles from field-grown <i>Desmodium</i>, many in the headspaces of both species, including volatiles previously reported to repel lepidopteran herbivores. In cage oviposition assays, FAW moths preferred to oviposit on maize over <i>Desmodium</i>, but not on maize further from, versus closer to <i>Desmodium</i> plants that were inaccessible to the moths, but sharing headspace. In flight tunnel assays, moths approached the headspace of maize more than shared headspaces of maize and <i>Desmodium</i>, but pairwise differences were often insignificant. Thus, headspaces of <i>Desmodium</i> species include volatiles that could repel FAW moths, and gravid moths were generally more attracted to maize and its headspace than to either <i>Desmodium</i> species or mixed maize-<i>Desmodium</i> headspaces. However, our results suggest that direct effects of <i>Desmodium</i> volatiles on FAW behavior are insufficient to explain reduced FAW infestation of maize under push-pull cultivation.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12510683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reassessing the link between adiposity and head and neck cancer: a Mendelian randomization study.","authors":"Fernanda Morales Berstein, Jasmine Khouja, Mark Gormley, Elmira Ebrahimi, Shama Virani, James D McKay, Paul Brennan, Tom G Richardson, Caroline L Relton, George Davey Smith, M Carolina Borges, Tom Dudding, Rebecca C Richmond","doi":"10.7554/eLife.106075","DOIUrl":"10.7554/eLife.106075","url":null,"abstract":"<p><strong>Background: </strong>Adiposity has been associated with an increased risk of head and neck cancer (HNC). Although body mass index (BMI) has been inversely associated with HNC risk among smokers, this is likely due to confounding. Previous Mendelian randomization (MR) studies could not fully discount causality between adiposity and HNC. Hence, we aimed to revisit this using the largest genome-wide association study (GWAS) of HNC available, which has more granular data on HNC subsites.</p><p><strong>Methods: </strong>We assessed the genetically predicted effects of BMI (N=806,834), waist-to-hip ratio (WHR; N=697,734) and waist circumference (N=462,166) on the risk of HNC (N=12,264 cases) and its subsites using a two-sample MR framework. We used inverse variance weighted (IVW) MR and multiple sensitivity analyses, including multivariable MR (MVMR), to explore the direct effects of the adiposity measures on HNC, while accounting for smoking behaviour (a well-known HNC risk factor).</p><p><strong>Results: </strong>In univariable MR, higher genetically predicted BMI increased the risk of overall HNC (IVW OR = 1.17 per 1-SD higher BMI, 95% CI 1.02-1.34). However, the IVW effect was attenuated when smoking was included in the MVMR model (OR accounting for comprehensive smoking index = 0.96 per 1-SD higher BMI, 95% CI 0.80-1.15). Furthermore, we did not find a link between genetically predicted WHR (IVW OR = 1.05 per 1-SD higher WHR, 95% CI 0.89-1.24) or waist circumference and HNC risk (IVW OR = 1.01 per 1-SD higher waist circumference, 95% CI 0.85-1.21).</p><p><strong>Conclusions: </strong>Our findings suggest that adiposity does not play a major role in HNC risk.</p><p><strong>Funding: </strong>FMB was supported by a Wellcome Trust PhD studentship in Molecular, Genetic and Lifecourse Epidemiology (224982/Z/22/Z). RCR was supported by a Cancer Research UK grant (C18281/A29019). MCB is supported by a University of Bristol Vice Chancellor's Fellowship, the British Heart Foundation (AA/18/1/34219) and the UK Medical Research Council (MC_UU_00032/5). GDS works within the MRC Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council (MC_UU_00032/1). CLR was supported by the Medical Research Council (MC_UU_00011/5) and by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). SV was funded by an EU Horizon 2020 grant (agreement number 825771) and NIDCR National Institutes of Dental and Craniofacial Health (R03DE030257). JK works in a unit that receives support from the University of Bristol, a Cancer Research UK grant (C18281/A29019) and the UK Medical Research Council (grant number: MC_UU_00032/7).</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12510682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diffusion MRS tracks distinct trajectories of neuronal development in the cerebellum and thalamus of rat neonates.","authors":"Clémence Ligneul, Lily Qiu, William T Clarke, Saad Jbabdi, Marco Palombo, Jason P Lerch","doi":"10.7554/eLife.96625","DOIUrl":"10.7554/eLife.96625","url":null,"abstract":"<p><p>It is currently impossible to non-invasively assess cerebellar cell structure during early development. Here, we propose a novel approach to non-invasively and longitudinally track cell-specific development using diffusion-weighted magnetic resonance spectroscopy (MRS) in combination with microstructural modelling. Tracking metabolite diffusion allows us to probe cell-specific developmental trajectories in the cerebellum and thalamus of healthy rat neonates from postnatal day (P) 5 to P30. Additionally, by comparing different analytical and biophysical microstructural models, we can follow the differential contribution of cell bodies and neurites during development. The thalamus serves as a control region to assess the sensitivity of our method to microstructural differences between the regions. We found significant differences between cerebellar and thalamic metabolites' diffusion properties. For most metabolites, the signal attenuation is stronger in the thalamus, suggesting less restricted diffusion compared to the cerebellum. There is also a trend for lower signal attenuation and lower apparent diffusion coefficients (ADCs) with increasing age, suggesting increasing restriction of metabolite diffusion. This is particularly striking for taurine in the thalamus. We use biophysical modelling to interpret these differences. We report a decreased sphere fraction (or an increased neurite fraction) with age for taurine and total creatine in the cerebellum, marking dendritic growth. Surprisingly, we also report a U-shape trend for segment length (the distance between two embranchments in a dendritic tree) in the cerebellum, agreeing with age-matching morphometry of openly available 3D-Purkinje reconstructions. Results demonstrate that diffusion-weighted MRS probes early cerebellar neuronal development non-invasively.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12510685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Partitioning changes in ecosystem productivity by effects of species interactions in biodiversity experiments.","authors":"Jing Tao, Charles A Nock, Eric B Searle, Shongming Huang, Rongzhou Man, Hua Yang, Grégoire T Freschet, Cyrille Violle, Ji Zheng","doi":"10.7554/eLife.98073","DOIUrl":"10.7554/eLife.98073","url":null,"abstract":"<p><p>Species interactions affect ecosystem productivity. Positive interactions (resource partitioning and facilitation) increase productivity while negative interactions (species interference) decrease productivity relative to the null expectations defined by monoculture yields. Effects of competitive interactions (resource competition) can be either positive or negative. Distinguishing effects of species interactions is therefore difficult, if not impossible, with current biodiversity experiments involving mixtures and full density monocultures. To partition changes in ecosystem productivity by effects of species interactions, we modify null expectations with competitive growth responses, i.e., proportional changes in individual size (biomass or volume) expected in mixture based on species differences in growth and competitive ability. We use partial density (species density in mixture) monocultures and the competitive exclusion principle to determine maximum competitive growth responses and full density monoculture yields to measure species ability to achieve maximum competitive growth responses in mixture. Deviations of observed yields from competitive expectations represent the effects of positive/negative species interactions, while the differences between competitive and null expectations reflect the effects of competitive interactions. We demonstrate the effectiveness of our competitive partitioning model in distinguishing effects of species interactions using both simulated and experimental species mixtures. Our competitive partitioning model enables meaningful assessments of species interactions at both species and community levels and helps disentangle underlying mechanisms of species interactions responsible for changes in ecosystem productivity and identify species mixtures that maximize positive effects.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12510681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Premature vision drives aberrant development of response properties in primary visual cortex.","authors":"Sophie V Griswold, Stephen D Van Hooser","doi":"10.7554/eLife.106513","DOIUrl":"10.7554/eLife.106513","url":null,"abstract":"<p><p>Development of the mammalian visual system is thought to proceed in two stages. In the first stage, before birth in primates and before eye opening in altricial mammals, spontaneous activity generated by the retina and cortex shapes visual brain circuits in an activity-dependent but experience-independent manner. In the second stage, visual activity generated by sensory experience refines receptive fields. Here, we investigated the consequences of altering this sequence of events by prematurely opening one or both eyes of ferrets and examining visual receptive fields in monocular cortex after the closure of the critical period for ocular dominance plasticity. We observed that many cells in animals with prematurely opened eyes exhibited low-pass temporal frequency tuning and increased temporal frequency bandwidths, and these cells showed slightly increased orientation and direction selectivity index values. Spontaneous activity was greatly elevated in both hemispheres following the premature opening of one or both eyes, suggesting a global change in circuit excitability that was not restricted to cells that viewed the world through the prematurely opened eye. No major changes were noted in spatial frequency tuning. These results suggest that premature visual experience alters circuit excitability and visual receptive fields, in particular with respect to temporal processing. We speculate that closed lids in altricial mammals serve to prevent visual experience until circuits are initially established and are ready to be refined by visual experience.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}