Nature neuroscience最新文献_第5页

Oligodendrocytes produce amyloid-β and contribute to plaque formation alongside neurons in Alzheimer’s disease model mice 在阿尔茨海默病模型小鼠体内，少突胶质细胞与神经元一起产生淀粉样蛋白-β并促进斑块形成

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-08-05 DOI: 10.1038/s41593-024-01730-3

Andrew Octavian Sasmita, Constanze Depp, Taisiia Nazarenko, Ting Sun, Sophie B. Siems, Erinne Cherisse Ong, Yakum B. Nkeh, Carolin Böhler, Xuan Yu, Bastian Bues, Lisa Evangelista, Shuying Mao, Barbara Morgado, Zoe Wu, Torben Ruhwedel, Swati Subramanian, Friederike Börensen, Katharina Overhoff, Lena Spieth, Stefan A. Berghoff, Katherine Rose Sadleir, Robert Vassar, Simone Eggert, Sandra Goebbels, Takashi Saito, Takaomi Saido, Gesine Saher, Wiebke Möbius, Gonçalo Castelo-Branco, Hans-Wolfgang Klafki, Oliver Wirths, Jens Wiltfang, Sarah Jäkel, Riqiang Yan, Klaus-Armin Nave

{"title":"Oligodendrocytes produce amyloid-β and contribute to plaque formation alongside neurons in Alzheimer’s disease model mice","authors":"Andrew Octavian Sasmita, Constanze Depp, Taisiia Nazarenko, Ting Sun, Sophie B. Siems, Erinne Cherisse Ong, Yakum B. Nkeh, Carolin Böhler, Xuan Yu, Bastian Bues, Lisa Evangelista, Shuying Mao, Barbara Morgado, Zoe Wu, Torben Ruhwedel, Swati Subramanian, Friederike Börensen, Katharina Overhoff, Lena Spieth, Stefan A. Berghoff, Katherine Rose Sadleir, Robert Vassar, Simone Eggert, Sandra Goebbels, Takashi Saito, Takaomi Saido, Gesine Saher, Wiebke Möbius, Gonçalo Castelo-Branco, Hans-Wolfgang Klafki, Oliver Wirths, Jens Wiltfang, Sarah Jäkel, Riqiang Yan, Klaus-Armin Nave","doi":"10.1038/s41593-024-01730-3","DOIUrl":"10.1038/s41593-024-01730-3","url":null,"abstract":"Amyloid-β (Aβ) is thought to be neuronally derived in Alzheimer’s disease (AD). However, transcripts of amyloid precursor protein (APP) and amyloidogenic enzymes are equally abundant in oligodendrocytes (OLs). By cell-type-specific deletion of Bace1 in a humanized knock-in AD model, APPNLGF, we demonstrate that OLs and neurons contribute to Aβ plaque burden. For rapid plaque seeding, excitatory projection neurons must provide a threshold level of Aβ. Ultimately, our findings are relevant for AD prevention and therapeutic strategies. In Alzheimer’s disease, neurons are considered the sole source of amyloid-β (Aβ) peptides that form plaques. Here the authors show that oligodendrocytes, the myelinating glial cells of the brain, also contribute to Aβ plaque burden alongside neurons.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01730-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891858","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}

引用次数: 0

Primary cilia signaling in astrocytes mediates development and regional-specific functional specification 星形胶质细胞中的初级纤毛信号介导发育和区域特异性功能分化

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-08-05 DOI: 10.1038/s41593-024-01726-z

Lizheng Wang, Qianqian Guo, Sandesh Acharya, Xiao Zheng, Vanessa Huynh, Brandon Whitmore, Askar Yimit, Mehr Malhotra, Siddharth Chatterji, Nicole Rosin, Elodie Labit, Colten Chipak, Kelsea Gorzo, Jordan Haidey, David A. Elliott, Tina Ram, Qingrun Zhang, Hedwich Kuipers, Grant Gordon, Jeff Biernaskie, Jiami Guo

{"title":"Primary cilia signaling in astrocytes mediates development and regional-specific functional specification","authors":"Lizheng Wang, Qianqian Guo, Sandesh Acharya, Xiao Zheng, Vanessa Huynh, Brandon Whitmore, Askar Yimit, Mehr Malhotra, Siddharth Chatterji, Nicole Rosin, Elodie Labit, Colten Chipak, Kelsea Gorzo, Jordan Haidey, David A. Elliott, Tina Ram, Qingrun Zhang, Hedwich Kuipers, Grant Gordon, Jeff Biernaskie, Jiami Guo","doi":"10.1038/s41593-024-01726-z","DOIUrl":"10.1038/s41593-024-01726-z","url":null,"abstract":"Astrocyte diversity is greatly influenced by local environmental modulation. Here we report that the majority of astrocytes across the mouse brain possess a singular primary cilium localized to the cell soma. Comparative single-cell transcriptomics reveals that primary cilia mediate canonical SHH signaling to modulate astrocyte subtype-specific core features in synaptic regulation, intracellular transport, energy and metabolism. Independent of canonical SHH signaling, primary cilia are important regulators of astrocyte morphology and intracellular signaling balance. Dendritic spine analysis and transcriptomics reveal that perturbation of astrocytic cilia leads to disruption of neuronal development and global intercellular connectomes in the brain. Mice with primary ciliary-deficient astrocytes show behavioral deficits in sensorimotor function, sociability, learning and memory. Our results uncover a critical role for primary cilia in transmitting local cues that drive the region-specific diversification of astrocytes within the developing brain. Astrocyte diversity is greatly influenced by local environmental modulation. Wang et al. report a critical role for astrocytic primary cilia in transmitting local cues that drive the region-specific diversification of astrocytes within the developing mouse brain.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891861","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}

引用次数: 0

An activity-regulated transcriptional program directly drives synaptogenesis 活动调控转录程序直接驱动突触发生

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-08-05 DOI: 10.1038/s41593-024-01728-x

Callista Yee, Yutong Xiao, Hongwen Chen, Anay R. Reddy, Bing Xu, Taylor N. Medwig-Kinney, Wan Zhang, Alan P. Boyle, Wendy A. Herbst, Yang Kevin Xiang, David Q. Matus, Kang Shen

{"title":"An activity-regulated transcriptional program directly drives synaptogenesis","authors":"Callista Yee, Yutong Xiao, Hongwen Chen, Anay R. Reddy, Bing Xu, Taylor N. Medwig-Kinney, Wan Zhang, Alan P. Boyle, Wendy A. Herbst, Yang Kevin Xiang, David Q. Matus, Kang Shen","doi":"10.1038/s41593-024-01728-x","DOIUrl":"10.1038/s41593-024-01728-x","url":null,"abstract":"Although the molecular composition and architecture of synapses have been widely explored, much less is known about what genetic programs directly activate synaptic gene expression and how they are modulated. Here, using Caenorhabditis elegans dopaminergic neurons, we reveal that EGL-43/MECOM and FOS-1/FOS control an activity-dependent synaptogenesis program. Loss of either factor severely reduces presynaptic protein expression. Both factors bind directly to promoters of synaptic genes and act together with CUT homeobox transcription factors to activate transcription. egl-43 and fos-1 mutually promote each other’s expression, and increasing the binding affinity of FOS-1 to the egl-43 locus results in increased presynaptic protein expression and synaptic function. EGL-43 regulates the expression of multiple transcription factors, including activity-regulated factors and developmental factors that define multiple aspects of dopaminergic identity. Together, we describe a robust genetic program underlying activity-regulated synapse formation during development. Neuronal activity contributes to synapse formation and plasticity. Here the authors demonstrate that activity stimulates developmental programs to directly modulate synapse formation.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01728-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891862","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}

引用次数: 0

A GnRH neuronal population in the olfactory bulb translates socially relevant odors into reproductive behavior in male mice 嗅球中的 GnRH 神经元群将雄性小鼠的社会相关气味转化为生殖行为

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-08-02 DOI: 10.1038/s41593-024-01724-1

Laurine Decoster, Sara Trova, Stefano Zucca, Janice Bulk, Ayden Gouveia, Gaetan Ternier, Tori Lhomme, Amandine Legrand, Sarah Gallet, Ulrich Boehm, Amanda Wyatt, Vanessa Wahl, Philipp Wartenberg, Erik Hrabovszky, Gergely Rácz, Federico Luzzati, Giulia Nato, Marco Fogli, Paolo Peretto, Sonja C. Schriever, Miriam Bernecker, Paul T. Pfluger, Sophie M. Steculorum, Serena Bovetti, Sowmyalakshmi Rasika, Vincent Prevot, Mauro S. B. Silva, Paolo Giacobini

{"title":"A GnRH neuronal population in the olfactory bulb translates socially relevant odors into reproductive behavior in male mice","authors":"Laurine Decoster, Sara Trova, Stefano Zucca, Janice Bulk, Ayden Gouveia, Gaetan Ternier, Tori Lhomme, Amandine Legrand, Sarah Gallet, Ulrich Boehm, Amanda Wyatt, Vanessa Wahl, Philipp Wartenberg, Erik Hrabovszky, Gergely Rácz, Federico Luzzati, Giulia Nato, Marco Fogli, Paolo Peretto, Sonja C. Schriever, Miriam Bernecker, Paul T. Pfluger, Sophie M. Steculorum, Serena Bovetti, Sowmyalakshmi Rasika, Vincent Prevot, Mauro S. B. Silva, Paolo Giacobini","doi":"10.1038/s41593-024-01724-1","DOIUrl":"10.1038/s41593-024-01724-1","url":null,"abstract":"Hypothalamic gonadotropin-releasing hormone (GnRH) neurons regulate fertility and integrate hormonal status with environmental cues to ensure reproductive success. Here we show that GnRH neurons in the olfactory bulb (GnRHOB) of adult mice can mediate social recognition. Specifically, we show that GnRHOB neurons extend neurites into the vomeronasal organ and olfactory epithelium and project to the median eminence. GnRHOB neurons in males express vomeronasal and olfactory receptors, are activated by female odors and mediate gonadotropin release in response to female urine. Male preference for female odors required the presence and activation of GnRHOB neurons, was impaired after genetic inhibition or ablation of these cells and relied on GnRH signaling in the posterodorsal medial amygdala. GnRH receptor expression in amygdala kisspeptin neurons appear to be required for GnRHOB neurons’ actions on male mounting behavior. Taken together, these results establish GnRHOB neurons as regulating fertility, sex recognition and mating in male mice. Studying GnRH neuroendocrine cells in the mouse olfactory bulb (GnRHOB neurons), Decoster et al. show that these cells respond to female odors and their activation regulates males’ female-odor preference and mating behavior.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141877414","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}

引用次数: 0

Population-level coding of avoidance learning in medial prefrontal cortex 内侧前额叶皮层中回避学习的群体级编码

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-07-29 DOI: 10.1038/s41593-024-01704-5

Benjamin Ehret, Roman Boehringer, Elizabeth A. Amadei, Maria R. Cervera, Christian Henning, Aniruddh R. Galgali, Valerio Mante, Benjamin F. Grewe

{"title":"Population-level coding of avoidance learning in medial prefrontal cortex","authors":"Benjamin Ehret, Roman Boehringer, Elizabeth A. Amadei, Maria R. Cervera, Christian Henning, Aniruddh R. Galgali, Valerio Mante, Benjamin F. Grewe","doi":"10.1038/s41593-024-01704-5","DOIUrl":"10.1038/s41593-024-01704-5","url":null,"abstract":"The medial prefrontal cortex (mPFC) has been proposed to link sensory inputs and behavioral outputs to mediate the execution of learned behaviors. However, how such a link is implemented has remained unclear. To measure prefrontal neural correlates of sensory stimuli and learned behaviors, we performed population calcium imaging during a new tone-signaled active avoidance paradigm in mice. We developed an analysis approach based on dimensionality reduction and decoding that allowed us to identify interpretable task-related population activity patterns. While a large fraction of tone-evoked activity was not informative about behavior execution, we identified an activity pattern that was predictive of tone-induced avoidance actions and did not occur for spontaneous actions with similar motion kinematics. Moreover, this avoidance-specific activity differed between distinct avoidance actions learned in two consecutive tasks. Overall, our results are consistent with a model in which mPFC contributes to the selection of goal-directed actions by transforming sensory inputs into specific behavioral outputs through distributed population-level computations. Ehret et al. uncover neural activity patterns in the prefrontal cortex that link sensory stimuli to learned behavioral responses by isolating interpretable activity patterns that are shared among mice performing the same task.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01704-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790948","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}

引用次数: 0

Centering cognitive neuroscience on task demands and generalization 认知神经科学以任务需求和推广为中心

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-07-29 DOI: 10.1038/s41593-024-01711-6

Matthias Nau, Alexandra C. Schmid, Simon M. Kaplan, Chris I. Baker, Dwight J. Kravitz

{"title":"Centering cognitive neuroscience on task demands and generalization","authors":"Matthias Nau, Alexandra C. Schmid, Simon M. Kaplan, Chris I. Baker, Dwight J. Kravitz","doi":"10.1038/s41593-024-01711-6","DOIUrl":"10.1038/s41593-024-01711-6","url":null,"abstract":"Cognitive neuroscience seeks generalizable theories explaining the relationship between behavioral, physiological and mental states. In pursuit of such theories, we propose a theoretical and empirical framework that centers on understanding task demands and the mutual constraints they impose on behavior and neural activity. Task demands emerge from the interaction between an agent’s sensory impressions, goals and behavior, which jointly shape the activity and structure of the nervous system on multiple spatiotemporal scales. Understanding this interaction requires multitask studies that vary more than one experimental component (for example, stimuli and instructions) combined with dense behavioral and neural sampling and explicit testing for generalization across tasks and data modalities. By centering task demands rather than mental processes that tasks are assumed to engage, this framework paves the way for the discovery of new generalizable concepts unconstrained by existing taxonomies, and moves cognitive neuroscience toward an action-oriented, dynamic and integrated view of the brain. Task demands are a primary determiner of behavior and neurophysiology. Here the authors discuss how understanding their influence through multitask studies and tests of generalization is the key to articulating novel cognitive neuroscience concepts.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790946","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}

引用次数: 0

Explaining dopamine through prediction errors and beyond 通过预测误差及其他因素解释多巴胺。

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-07-25 DOI: 10.1038/s41593-024-01705-4

Samuel J. Gershman, John A. Assad, Sandeep Robert Datta, Scott W. Linderman, Bernardo L. Sabatini, Naoshige Uchida, Linda Wilbrecht

{"title":"Explaining dopamine through prediction errors and beyond","authors":"Samuel J. Gershman, John A. Assad, Sandeep Robert Datta, Scott W. Linderman, Bernardo L. Sabatini, Naoshige Uchida, Linda Wilbrecht","doi":"10.1038/s41593-024-01705-4","DOIUrl":"10.1038/s41593-024-01705-4","url":null,"abstract":"The most influential account of phasic dopamine holds that it reports reward prediction errors (RPEs). The RPE-based interpretation of dopamine signaling is, in its original form, probably too simple and fails to explain all the properties of phasic dopamine observed in behaving animals. This Perspective helps to resolve some of the conflicting interpretations of dopamine that currently exist in the literature. We focus on the following three empirical challenges to the RPE theory of dopamine: why does dopamine (1) ramp up as animals approach rewards, (2) respond to sensory and motor features and (3) influence action selection? We argue that the prediction error concept, once it has been suitably modified and generalized based on an analysis of each computational problem, answers each challenge. Nonetheless, there are a number of additional empirical findings that appear to demand fundamentally different theoretical explanations beyond encoding RPE. Therefore, looking forward, we discuss the prospects for a unifying theory that respects the diversity of dopamine signaling and function as well as the complex circuitry that both underlies and responds to dopaminergic transmission. The hypothesis that dopamine reports reward prediction errors has been both influential and controversial. This Perspective characterizes the present state of evidence, indicating where it succeeds and where it falls short. A complete account of dopamine will probably need to move beyond the reward prediction error hypothesis while retaining its core explanatory power.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760009","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}

引用次数: 0

Author Correction: Sharpened cochlear tuning in a mouse with a genetically modified tectorial membrane 作者更正：转基因胸膜小鼠耳蜗调谐能力增强

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-07-24 DOI: 10.1038/s41593-024-01727-y

Ian J. Russell, P. Kevin Legan, Victoria A. Lukashkina, Andrei N. Lukashkin, Richard J. Goodyear, Guy P. Richardson

引用次数: 0

Nested compressed co-representations of multiple sequential experiences during sleep 睡眠中多重连续经验的嵌套压缩共表征

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-07-19 DOI: 10.1038/s41593-024-01703-6

Kefei Liu, Jeremie Sibille, George Dragoi

{"title":"Nested compressed co-representations of multiple sequential experiences during sleep","authors":"Kefei Liu, Jeremie Sibille, George Dragoi","doi":"10.1038/s41593-024-01703-6","DOIUrl":"10.1038/s41593-024-01703-6","url":null,"abstract":"Animals encounter and remember multiple experiences daily. During sleep, hippocampal neuronal ensembles replay past experiences and preplay future ones. Although most previous studies investigated p/replay of a single experience, it remains unclear how the hippocampus represents many experiences without major interference during sleep. By monitoring hippocampal neuronal ensembles as rats encountered 15 distinct linear track experiences, we uncovered principles for efficient multi-experience compressed p/replay representation. First, we found a serial position effect whereby the earliest and the most recent experiences had the strongest representations. Second, distinct experiences were co-represented in a multiplexed, flickering manner during nested p/replay events, which greatly enhanced the network’s representational capacity. Third, spatially contiguous and disjunct track pairs were bound together into contiguous conjunctive representations during sleep. Finally, sequences spanning day-long multi-track experiences were p/replayed at hyper-compressed ratios during sleep. These coding schemes efficiently parallelize, bind and compress multiple sequential representations with reduced interference and enhanced capacity during sleep. Liu et al. unraveled several hippocampal neural ensemble coding schemes that efficiently represent numerous daily experiences during sleep by prioritizing the most recent and earliest events, multiplexing co-representations and compressing day-long sequences.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727579","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}

引用次数: 0

Higher-order interactions between hippocampal CA1 neurons are disrupted in amnestic mice 失忆症小鼠海马 CA1 神经元之间的高阶交互作用受到破坏

IF 21.2 1区医学

Nature neuroscience Pub Date : 2024-07-19 DOI: 10.1038/s41593-024-01713-4

Chen Yan, Valentina Mercaldo, Alexander D. Jacob, Emily Kramer, Andrew Mocle, Adam I. Ramsaran, Lina Tran, Asim J. Rashid, Sungmo Park, Nathan Insel, A. David Redish, Paul W. Frankland, Sheena A. Josselyn

{"title":"Higher-order interactions between hippocampal CA1 neurons are disrupted in amnestic mice","authors":"Chen Yan, Valentina Mercaldo, Alexander D. Jacob, Emily Kramer, Andrew Mocle, Adam I. Ramsaran, Lina Tran, Asim J. Rashid, Sungmo Park, Nathan Insel, A. David Redish, Paul W. Frankland, Sheena A. Josselyn","doi":"10.1038/s41593-024-01713-4","DOIUrl":"10.1038/s41593-024-01713-4","url":null,"abstract":"Across systems, higher-order interactions between components govern emergent dynamics. Here we tested whether contextual threat memory retrieval in mice relies on higher-order interactions between dorsal CA1 hippocampal neurons requiring learning-induced dendritic spine plasticity. We compared population-level Ca2+ transients as wild-type mice (with intact learning-induced spine plasticity and memory) and amnestic mice (TgCRND8 mice with high levels of amyloid-β and deficits in learning-induced spine plasticity and memory) were tested for memory. Using machine-learning classifiers with different capacities to use input data with complex interactions, our findings indicate complex neuronal interactions in the memory representation of wild-type, but not amnestic, mice. Moreover, a peptide that partially restored learning-induced spine plasticity also restored the statistical complexity of the memory representation and memory behavior in Tg mice. These findings provide a previously missing bridge between levels of analysis in memory research, linking receptors, spines, higher-order neuronal dynamics and behavior. Coordinated neuronal activity may mediate memory in hippocampal CA1. Here, the authors use an array of machine-learning classifiers to reveal how higher-order population dynamics and learning-induced spine plasticity are disrupted in amnestic mice.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727578","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}

引用次数: 0