eLife最新文献

{"title":"Correction: Gene regulatory patterning codes in early cell fate specification of the <i>C. elegans</i> embryo.","authors":"Alison G Cole, Tamar Hashinshony, Zhuo Du, Itai Yanai","doi":"10.7554/eLife.106163","DOIUrl":"10.7554/eLife.106163","url":null,"abstract":"<p><p></p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046005","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":"Discriminating neural ensemble patterns through dendritic computations in randomly connected feedforward networks.","authors":"Bhanu Priya Somashekar, Upinder Singh Bhalla","doi":"10.7554/eLife.100664","DOIUrl":"10.7554/eLife.100664","url":null,"abstract":"<p><p>Co-active or temporally ordered neural ensembles are a signature of salient sensory, motor, and cognitive events. Local convergence of such patterned activity as synaptic clusters on dendrites could help single neurons harness the potential of dendritic nonlinearities to decode neural activity patterns. We combined theory and simulations to assess the likelihood of whether projections from neural ensembles could converge onto synaptic clusters even in networks with random connectivity. Using rat hippocampal and cortical network statistics, we show that clustered convergence of axons from three to four different co-active ensembles is likely even in randomly connected networks, leading to representation of arbitrary input combinations in at least 10 target neurons in a 100,000 population. In the presence of larger ensembles, spatiotemporally ordered convergence of three to five axons from temporally ordered ensembles is also likely. These active clusters result in higher neuronal activation in the presence of strong dendritic nonlinearities and low background activity. We mathematically and computationally demonstrate a tight interplay between network connectivity, spatiotemporal scales of subcellular electrical and chemical mechanisms, dendritic nonlinearities, and uncorrelated background activity. We suggest that dendritic clustered and sequence computation is pervasive, but its expression as somatic selectivity requires confluence of physiology, background activity, and connectomics.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032647","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":"Dynamics and regulatory roles of RNA m⁶A methylation in unbalanced genomes.","authors":"Shuai Zhang, Ruixue Wang, Kun Luo, Shipeng Gu, Xinyu Liu, Junhan Wang, Ludan Zhang, Lin Sun","doi":"10.7554/eLife.100144","DOIUrl":"10.7554/eLife.100144","url":null,"abstract":"<p><p><i>N</i>⁶-methyladenosine (m⁶A) in eukaryotic RNA is an epigenetic modification that is critical for RNA metabolism, gene expression regulation, and the development of organisms. Aberrant expression of m⁶A components appears in a variety of human diseases. RNA m⁶A modification in <i>Drosophila</i> has proven to be involved in sex determination regulated by <i>Sxl</i> and may affect X chromosome expression through the MSL complex. The dosage-related effects under the condition of genomic imbalance (i.e. aneuploidy) are related to various epigenetic regulatory mechanisms. Here, we investigated the roles of RNA m⁶A modification in unbalanced genomes using aneuploid <i>Drosophila</i>. The results showed that the expression of m⁶A components changed significantly under genomic imbalance, and affected the abundance and genome-wide distribution of m⁶A, which may be related to the developmental abnormalities of aneuploids. The relationships between methylation status and classical dosage effect, dosage compensation, and inverse dosage effect were also studied. In addition, we demonstrated that RNA m⁶A methylation may affect dosage-dependent gene regulation through dosage-sensitive modifiers, alternative splicing, the MSL complex, and other processes. More interestingly, there seems to be a close relationship between MSL complex and RNA m⁶A modification. It is found that ectopically overexpressed MSL complex, especially the levels of H4K16Ac through MOF, could influence the expression levels of m⁶A modification and genomic imbalance may be involved in this interaction. We found that m⁶A could affect the levels of H4K16Ac through MOF, a component of the MSL complex, and that genomic imbalance may be involved in this interaction. Altogether, our work reveals the dynamic and regulatory role of RNA m⁶A modification in unbalanced genomes, and may shed new light on the mechanisms of aneuploidy-related developmental abnormalities and diseases.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032650","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":"A split-GAL4 driver line resource for <i>Drosophila</i> neuron types.","authors":"Geoffrey W Meissner, Allison Vannan, Jennifer Jeter, Kari Close, Gina M DePasquale, Zachary Dorman, Kaitlyn Forster, Jaye Anne Beringer, Theresa Gibney, Joanna H Hausenfluck, Yisheng He, Kristin Henderson, Lauren Johnson, Rebecca M Johnston, Gudrun Ihrke, Nirmala A Iyer, Rachel Lazarus, Kelley Lee, Hsing-Hsi Li, Hua-Peng Liaw, Brian Melton, Scott Miller, Reeham Motaher, Alexandra Novak, Omotara Ogundeyi, Alyson Petruncio, Jacquelyn Price, Sophia Protopapas, Susana Tae, Jennifer Taylor, Rebecca Vorimo, Brianna Yarbrough, Kevin Xiankun Zeng, Christopher T Zugates, Heather Dionne, Claire Angstadt, Kelly Ashley, Amanda Cavallaro, Tam Dang, Guillermo A Gonzalez, Karen L Hibbard, Cuizhen Huang, Jui-Chun Kao, Todd Laverty, Monti Mercer, Brenda Perez, Scarlett Rose Pitts, Danielle Ruiz, Viruthika Vallanadu, Grace Zhiyu Zheng, Cristian Goina, Hideo Otsuna, Konrad Rokicki, Robert R Svirskas, Han S J Cheong, Michael-John Dolan, Erica Ehrhardt, Kai Feng, Basel E I Galfi, Jens Goldammer, Stephen J Huston, Nan Hu, Masayoshi Ito, Claire McKellar, Ryo Minegishi, Shigehiro Namiki, Aljoscha Nern, Catherine E Schretter, Gabriella R Sterne, Lalanti Venkatasubramanian, Kaiyu Wang, Tanya Wolff, Ming Wu, Reed George, Oz Malkesman, Yoshinori Aso, Gwyneth M Card, Barry J Dickson, Wyatt Korff, Kei Ito, James W Truman, Marta Zlatic, Gerald M Rubin","doi":"10.7554/eLife.98405","DOIUrl":"10.7554/eLife.98405","url":null,"abstract":"<p><p>Techniques that enable precise manipulations of subsets of neurons in the fly central nervous system (CNS) have greatly facilitated our understanding of the neural basis of behavior. Split-GAL4 driver lines allow specific targeting of cell types in <i>Drosophila melanogaster</i> and other species. We describe here a collection of 3060 lines targeting a range of cell types in the adult <i>Drosophila</i> CNS and 1373 lines characterized in third-instar larvae. These tools enable functional, transcriptomic, and proteomic studies based on precise anatomical targeting. NeuronBridge and other search tools relate light microscopy images of these split-GAL4 lines to connectomes reconstructed from electron microscopy images. The collections are the result of screening over 77,000 split hemidriver combinations. Previously published and new lines are included, all validated for driver expression and curated for optimal cell-type specificity across diverse cell types. In addition to images and fly stocks for these well-characterized lines, we make available 300,000 new 3D images of other split-GAL4 lines.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032645","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":"Automated cell annotation in multi-cell images using an improved CRF_ID algorithm.","authors":"Hyun Jee Lee, Jingting Liang, Shivesh Chaudhary, Sihoon Moon, Zikai Yu, Taihong Wu, He Liu, Myung-Kyu Choi, Yun Zhang, Hang Lu","doi":"10.7554/eLife.89050","DOIUrl":"10.7554/eLife.89050","url":null,"abstract":"<p><p>Cell identification is an important yet difficult process in data analysis of biological images. Previously, we developed an automated cell identification method called CRF_ID and demonstrated its high performance in <i>Caenorhabditis elegans</i> whole-brain images (Chaudhary et al., 2021). However, because the method was optimized for whole-brain imaging, comparable performance could not be guaranteed for application in commonly used <i>C. elegans</i> multi-cell images that display a subpopulation of cells. Here, we present an advancement, CRF_ID 2.0, that expands the generalizability of the method to multi-cell imaging beyond whole-brain imaging. To illustrate the application of the advance, we show the characterization of CRF_ID 2.0 in multi-cell imaging and cell-specific gene expression analysis in <i>C. elegans</i>. This work demonstrates that high-accuracy automated cell annotation in multi-cell imaging can expedite cell identification and reduce its subjectivity in <i>C. elegans</i> and potentially other biological images of various origins.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"12 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032652","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":"Projections from thalamic nucleus reuniens to hippocampal CA1 area participate in context fear extinction by affecting extinction-induced molecular remodeling of excitatory synapses.","authors":"Magdalena Ziółkowska, Narges Sotoudeh, Anna Cały, Monika Puchalska, Roberto Pagano, Malgorzata Alicja Śliwińska, Ahmad Salamian, Kasia Radwanska","doi":"10.7554/eLife.101736","DOIUrl":"10.7554/eLife.101736","url":null,"abstract":"<p><p>The ability to extinguish contextual fear in a changing environment is crucial for animal survival. Recent data support the role of the thalamic nucleus reuniens (RE) and its projections to the dorsal hippocampal CA1 area (RE→dCA1) in this process. However, it remains poorly understood how RE impacts dCA1 neurons during contextual fear extinction (CFE). Here, we reveal that the RE→dCA1 pathway contributes to the extinction of contextual fear by affecting CFE-induced molecular remodeling of excitatory synapses. Anatomical tracing and chemogenetic manipulation in mice demonstrate that RE neurons form synapses and regulate synaptic transmission in the stratum oriens (SO) and lacunosum-moleculare (SLM) of the dCA1 area, but not in the stratum radiatum (SR). We also observe CFE-specific structural changes of excitatory synapses and expression of the synaptic scaffold protein, PSD-95, in both strata innervated by RE, but not in SR. Interestingly, only the changes in SLM are specific for the dendrites innervated by RE. To further support the role of the RE→dCA1 projection in CFE, we demonstrate that brief chemogenetic inhibition of the RE→dCA1 pathway during a CFE session persistently impairs the formation of CFE memory and CFE-induced changes of PSD-95 levels in SLM. Thus, our data indicate that RE participates in CFE by regulating CFE-induced molecular remodeling of dCA1 synapses.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022858","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":"Multisensory integration operates on correlated input from unimodal transient channels.","authors":"Cesare V Parise, Marc O Ernst","doi":"10.7554/eLife.90841","DOIUrl":"10.7554/eLife.90841","url":null,"abstract":"<p><p>Audiovisual information reaches the brain via both sustained and transient input channels, representing signals' intensity over time or changes thereof, respectively. To date, it is unclear to what extent transient and sustained input channels contribute to the combined percept obtained through multisensory integration. Based on the results of two novel psychophysical experiments, here we demonstrate the importance of the transient (instead of the sustained) channel for the integration of audiovisual signals. To account for the present results, we developed a biologically inspired, general-purpose model for multisensory integration, the multisensory correlation detectors, which combines correlated input from unimodal transient channels. Besides accounting for the results of our psychophysical experiments, this model could quantitatively replicate several recent findings in multisensory research, as tested against a large collection of published datasets. In particular, the model could simultaneously account for the perceived timing of audiovisual events, multisensory facilitation in detection tasks, causality judgments, and optimal integration. This study demonstrates that several phenomena in multisensory research that were previously considered unrelated, all stem from the integration of correlated input from unimodal transient channels.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"12 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002345","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":"How a gene fuels ear infections.","authors":"Sedigheh Delmaghani, Aziz El-Amraoui","doi":"10.7554/eLife.105612","DOIUrl":"10.7554/eLife.105612","url":null,"abstract":"<p><p>The DYRK1A enzyme is a pivotal contributor to frequent and severe episodes of otitis media in Down syndrome, positioning it as a promising target for therapeutic interventions.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002341","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":"Multi-study fMRI outlooks on subcortical BOLD responses in the stop-signal paradigm.","authors":"Scott Isherwood, Sarah A Kemp, Steven Miletić, Niek Stevenson, Pierre-Louis Bazin, Birte Forstmann","doi":"10.7554/eLife.88652","DOIUrl":"10.7554/eLife.88652","url":null,"abstract":"<p><p>This study investigates the functional network underlying response inhibition in the human brain, particularly the role of the basal ganglia in successful action cancellation. Functional magnetic resonance imaging (fMRI) approaches have frequently used the stop-signal task to examine this network. We merge five such datasets, using a novel aggregatory method allowing the unification of raw fMRI data across sites. This meta-analysis, along with other recent aggregatory fMRI studies, does not find evidence for the innervation of the <i>hyperdirect</i> or <i>indirect</i> cortico-basal-ganglia pathways in successful response inhibition. What we do find, is large subcortical activity profiles for <i>failed stop</i> trials. We discuss possible explanations for the mismatch of findings between the fMRI results presented here and results from other research modalities that have implicated nodes of the basal ganglia in successful inhibition. We also highlight the substantial effect smoothing can have on the conclusions drawn from task-specific general linear models. First and foremost, this study presents a proof of concept for meta-analytical methods that enable the merging of extensive, unprocessed, or unreduced datasets. It demonstrates the significant potential that open-access data sharing can offer to the research community. With an increasing number of datasets being shared publicly, researchers will have the ability to conduct meta-analyses on more than just summary data.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"12 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002248","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":"A double dissociation between semantic and spatial cognition in visual to default network pathways.","authors":"Tirso R J Gonzalez Alam, Katya Krieger-Redwood, Dominika Varga, Zhiyao Gao, Aidan J Horner, Tom Hartley, Michel Thiebaut de Schotten, Magdalena Sliwinska, David Pitcher, Daniel S Margulies, Jonathan Smallwood, Elizabeth Jefferies","doi":"10.7554/eLife.94902","DOIUrl":"10.7554/eLife.94902","url":null,"abstract":"<p><p>Processing pathways between sensory and default mode network (DMN) regions support recognition, navigation, and memory but their organisation is not well understood. We show that functional subdivisions of visual cortex and DMN sit at opposing ends of parallel streams of information processing that support visually mediated semantic and spatial cognition, providing convergent evidence from univariate and multivariate task responses, intrinsic functional and structural connectivity. Participants learned virtual environments consisting of buildings populated with objects, drawn from either a single semantic category or multiple categories. Later, they made semantic and spatial context decisions about these objects and buildings during functional magnetic resonance imaging. A lateral ventral occipital to fronto-temporal DMN pathway was primarily engaged by semantic judgements, while a medial visual to medial temporal DMN pathway supported spatial context judgements. These pathways had distinctive locations in functional connectivity space: the semantic pathway was both further from unimodal systems and more balanced between visual and auditory-motor regions compared with the spatial pathway. When semantic and spatial context information could be integrated (in buildings containing objects from a single category), regions at the intersection of these pathways responded, suggesting that parallel processing streams interact at multiple levels of the cortical hierarchy to produce coherent memory-guided cognition.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002286","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}