eLife最新文献 - Book学术

Projections from thalamic nucleus reuniens to hippocampal CA1 area participate in context fear extinction by affecting extinction-induced molecular remodeling of excitatory synapses.

IF 6.4 1区生物学

eLife Pub Date : 2025-01-23 DOI: 10.7554/eLife.101736

Magdalena Ziółkowska, Narges Sotoudeh, Anna Cały, Monika Puchalska, Roberto Pagano, Malgorzata Alicja Śliwińska, Ahmad Salamian, Kasia Radwanska

{"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":"https://doi.org/10.7554/eLife.101736","url":null,"abstract":"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.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

How a gene fuels ear infections. 基因如何引发耳部感染。

IF 6.4 1区生物学

eLife Pub Date : 2025-01-22 DOI: 10.7554/eLife.105612

Sedigheh Delmaghani, Aziz El-Amraoui

引用次数: 0

Multisensory integration operates on correlated input from unimodal transient channels. 多感觉整合在单峰瞬时通道的相关输入上运作。

IF 6.4 1区生物学

eLife Pub Date : 2025-01-22 DOI: 10.7554/eLife.90841

Cesare V Parise, Marc O Ernst

{"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":"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.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"12 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multi-study fMRI outlooks on subcortical BOLD responses in the stop-signal paradigm. 在停止-信号范式下，皮质下BOLD反应的多研究fMRI前景。

IF 6.4 1区生物学

eLife Pub Date : 2025-01-22 DOI: 10.7554/eLife.88652

Scott Isherwood, Sarah A Kemp, Steven Miletić, Niek Stevenson, Pierre-Louis Bazin, Birte Forstmann

{"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":"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 hyperdirect or indirect cortico-basal-ganglia pathways in successful response inhibition. What we do find, is large subcortical activity profiles for failed stop 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.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"12 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A double dissociation between semantic and spatial cognition in visual to default network pathways. 视觉到默认网络通路中语义和空间认知的双重分离。

IF 6.4 1区生物学

eLife Pub Date : 2025-01-22 DOI: 10.7554/eLife.94902

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

{"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":"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.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Endopiriform neurons projecting to ventral CA1 are a critical node for recognition memory. 内梨状神经元投射到腹侧CA1是识别记忆的关键节点。

IF 6.4 1区生物学

eLife Pub Date : 2025-01-21 DOI: 10.7554/eLife.99642

Naoki Yamawaki, Hande Login, Solbjørg Østergaard Feld-Jakobsen, Bernadett Mercedesz Molnar, Mads Zippor Kirkegaard, Maria Moltesen, Aleksandra Okrasa, Jelena Radulovic, Asami Tanimura

{"title":"Endopiriform neurons projecting to ventral CA1 are a critical node for recognition memory.","authors":"Naoki Yamawaki, Hande Login, Solbjørg Østergaard Feld-Jakobsen, Bernadett Mercedesz Molnar, Mads Zippor Kirkegaard, Maria Moltesen, Aleksandra Okrasa, Jelena Radulovic, Asami Tanimura","doi":"10.7554/eLife.99642","DOIUrl":"10.7554/eLife.99642","url":null,"abstract":"The claustrum complex is viewed as fundamental for higher-order cognition; however, the circuit organization and function of its neuroanatomical subregions are not well understood. We demonstrated that some of the key roles of the CLA complex can be attributed to the connectivity and function of a small group of neurons in its ventral subregion, the endopiriform (EN). We identified a subpopulation of EN neurons by their projection to the ventral CA1 (ENvCA1-proj. neurons), embedded in recurrent circuits with other EN neurons and the piriform cortex. Although the ENvCA1-proj. neuron activity was biased toward novelty across stimulus categories, their chemogenetic inhibition selectively disrupted the memory-guided but not innate responses of mice to novelty. Based on our functional connectivity analysis, we suggest that ENvCA1-proj. neurons serve as an essential node for recognition memory through recurrent circuits mediating sustained attention to novelty, and through feed-forward inhibition of distal vCA1 neurons shifting memory-guided behavior from familiarity to novelty.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002313","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}

引用次数: 0

Mixed representations of choice direction and outcome by GABA/glutamate cotransmitting neurons in the entopeduncular nucleus. 脑核内GABA/谷氨酸共传递神经元对选择方向和结果的混合表征。

IF 6.4 1区生物学

eLife Pub Date : 2025-01-21 DOI: 10.7554/eLife.100488

Julianna Locantore, Yijun Liu, Jesse White, Janet Berrios Wallace, Celia Beron, Emily Kraft, Bernardo Sabatini, Michael Wallace

{"title":"Mixed representations of choice direction and outcome by GABA/glutamate cotransmitting neurons in the entopeduncular nucleus.","authors":"Julianna Locantore, Yijun Liu, Jesse White, Janet Berrios Wallace, Celia Beron, Emily Kraft, Bernardo Sabatini, Michael Wallace","doi":"10.7554/eLife.100488","DOIUrl":"10.7554/eLife.100488","url":null,"abstract":"The basal ganglia (BG) are an evolutionarily conserved and phylogenetically old set of sub-cortical nuclei that guide action selection, evaluation, and reinforcement. The entopeduncular nucleus (EP) is a major BG output nucleus that contains a population of GABA/glutamate cotransmitting neurons (EPSst+) that specifically target the lateral habenula (LHb) and whose function in behavior remains mysterious. Here, we use a probabilistic switching task that requires an animal to maintain flexible relationships between action selection and evaluation to examine when and how GABA/glutamate cotransmitting neurons contribute to behavior. We find that EPSst+ neurons are strongly engaged during this task and show bidirectional changes in activity during the choice and outcome periods of a trial. We then tested the effects of either permanently blocking cotransmission or modifying the GABA/glutamate ratio on behavior in well-trained animals. Neither manipulation produced detectable changes in behavior despite significant changes in synaptic transmission in the LHb, demonstrating that the outputs of these neurons are not required for ongoing action-outcome updating in a probabilistic switching task.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002318","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}

引用次数: 0

Syngeneic natural killer cell therapy activates dendritic and T cells in metastatic lungs and effectively treats low-burden metastases. 同基因自然杀伤细胞疗法激活转移性肺中的树突状细胞和T细胞，有效治疗低负荷转移。

IF 6.4 1区生物学

eLife Pub Date : 2025-01-21 DOI: 10.7554/eLife.99010

Shih-Wen Huang, Yein-Gei Lai, Hao-Ting Liao, Chin-Ling Chang, Ruo-Yu Ma, Yung-Hsiang Chen, Yae-Huei Liou, Zhen-Qi Wu, Yu-Chen Wu, Ko-Jiunn Liu, Yen-Tsung Huang, Jen-Lung Yang, Ming-Shen Dai, Nan-Shih Liao

{"title":"Syngeneic natural killer cell therapy activates dendritic and T cells in metastatic lungs and effectively treats low-burden metastases.","authors":"Shih-Wen Huang, Yein-Gei Lai, Hao-Ting Liao, Chin-Ling Chang, Ruo-Yu Ma, Yung-Hsiang Chen, Yae-Huei Liou, Zhen-Qi Wu, Yu-Chen Wu, Ko-Jiunn Liu, Yen-Tsung Huang, Jen-Lung Yang, Ming-Shen Dai, Nan-Shih Liao","doi":"10.7554/eLife.99010","DOIUrl":"10.7554/eLife.99010","url":null,"abstract":"Natural killer (NK) cells can control metastasis through cytotoxicity and IFN-γ production independently of T cells in experimental metastasis mouse models. The inverse correlation between NK activity and metastasis incidence supports a critical role for NK cells in human metastatic surveillance. However, autologous NK cell therapy has shown limited benefit in treating patients with metastatic solid tumors. Using a spontaneous metastasis mouse model of MHC-I+ breast cancer, we found that transfer of IL-15/IL-12-conditioned syngeneic NK cells after primary tumor resection promoted long-term survival of mice with low metastatic burden and induced a tumor-specific protective T cell response that is essential for the therapeutic effect. Furthermore, NK cell transfer augments activation of conventional dendritic cells (cDCs), Foxp3-CD4+ T cells and stem cell-like CD8+ T cells in metastatic lungs, to which IFN-γ of the transferred NK cells contributes significantly. These results imply direct interactions between transferred NK cells and endogenous cDCs to enhance T cell activation. We conducted an investigator-initiated clinical trial of autologous NK cell therapy in six patients with advanced cancer and observed that the NK cell therapy was safe and showed signs of effectiveness. These findings indicate that autologous NK cell therapy is effective in treating established low burden metastases of MHC-I+ tumor cells by activating the cDC-T cell axis at metastatic sites.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002327","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}

引用次数: 0

Effects of noise and metabolic cost on cortical task representations. 噪声和代谢代价对皮层任务表征的影响。

IF 6.4 1区生物学

eLife Pub Date : 2025-01-21 DOI: 10.7554/eLife.94961

Jake Patrick Stroud, Michal Wojcik, Kristopher Torp Jensen, Makoto Kusunoki, Mikiko Kadohisa, Mark J Buckley, John Duncan, Mark G Stokes, Mate Lengyel

{"title":"Effects of noise and metabolic cost on cortical task representations.","authors":"Jake Patrick Stroud, Michal Wojcik, Kristopher Torp Jensen, Makoto Kusunoki, Mikiko Kadohisa, Mark J Buckley, John Duncan, Mark G Stokes, Mate Lengyel","doi":"10.7554/eLife.94961","DOIUrl":"10.7554/eLife.94961","url":null,"abstract":"Cognitive flexibility requires both the encoding of task-relevant and the ignoring of task-irrelevant stimuli. While the neural coding of task-relevant stimuli is increasingly well understood, the mechanisms for ignoring task-irrelevant stimuli remain poorly understood. Here, we study how task performance and biological constraints jointly determine the coding of relevant and irrelevant stimuli in neural circuits. Using mathematical analyses and task-optimized recurrent neural networks, we show that neural circuits can exhibit a range of representational geometries depending on the strength of neural noise and metabolic cost. By comparing these results with recordings from primate prefrontal cortex (PFC) over the course of learning, we show that neural activity in PFC changes in line with a minimal representational strategy. Specifically, our analyses reveal that the suppression of dynamically irrelevant stimuli is achieved by activity-silent, sub-threshold dynamics. Our results provide a normative explanation as to why PFC implements an adaptive, minimal representational strategy.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002308","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}

引用次数: 0

Tripartite organization of brain state dynamics underlying spoken narrative comprehension. 口语叙事理解中脑状态动态的三方组织。

IF 6.4 1区生物学

eLife Pub Date : 2025-01-21 DOI: 10.7554/eLife.99997

Lanfang Liu, Jiahao Jiang, Hehui Li, Guosheng Ding

{"title":"Tripartite organization of brain state dynamics underlying spoken narrative comprehension.","authors":"Lanfang Liu, Jiahao Jiang, Hehui Li, Guosheng Ding","doi":"10.7554/eLife.99997","DOIUrl":"10.7554/eLife.99997","url":null,"abstract":"Speech comprehension involves the dynamic interplay of multiple cognitive processes, from basic sound perception, to linguistic encoding, and finally to complex semantic-conceptual interpretations. How the brain handles the diverse streams of information processing remains poorly understood. Applying Hidden Markov Modeling to fMRI data obtained during spoken narrative comprehension, we reveal that the whole brain networks predominantly oscillate within a tripartite latent state space. These states are, respectively, characterized by high activities in the sensory-motor (State #1), bilateral temporal (State #2), and default mode networks (DMN; State #3) regions, with State #2 acting as a transitional hub. The three states are selectively modulated by the acoustic, word-level semantic, and clause-level semantic properties of the narrative. Moreover, the alignment with both the best performer and the group-mean in brain state expression can predict participants' narrative comprehension scores measured from the post-scan recall. These results are reproducible with different brain network atlas and generalizable to two datasets consisting of young and older adults. Our study suggests that the brain underlies narrative comprehension by switching through a tripartite state space, with each state probably dedicated to a specific component of language faculty, and effective narrative comprehension relies on engaging those states in a timely manner.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002332","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}

引用次数: 0