Pub Date : 2024-06-07DOI: 10.1038/s41593-024-01678-4
Daniel Holl, Wing Fung Hau, Anais Julien, Shervin Banitalebi, Jannis Kalkitsas, Soniya Savant, Enric Llorens-Bobadilla, Yann Herault, Guillaume Pavlovic, Mahmood Amiry-Moghaddam, David Oliveira Dias, Christian Göritz
Fibrotic scar tissue formation occurs in humans and mice. The fibrotic scar impairs tissue regeneration and functional recovery. However, the origin of scar-forming fibroblasts is unclear. Here, we show that stromal fibroblasts forming the fibrotic scar derive from two populations of perivascular cells after spinal cord injury (SCI) in adult mice of both sexes. We anatomically and transcriptionally identify the two cell populations as pericytes and perivascular fibroblasts. Fibroblasts and pericytes are enriched in the white and gray matter regions of the spinal cord, respectively. Both cell populations are recruited in response to SCI and inflammation. However, their contribution to fibrotic scar tissue depends on the location of the lesion. Upon injury, pericytes and perivascular fibroblasts become activated and transcriptionally converge on the generation of stromal myofibroblasts. Our results show that pericytes and perivascular fibroblasts contribute to the fibrotic scar in a region-dependent manner. The origin and composition of stromal fibroblasts in the fibrotic CNS scar are unclear. Here, the authors demonstrate that pericytes and perivascular fibroblasts contribute to fibrotic scarring following spinal cord injury in mice in a region-dependent manner.
{"title":"Distinct origin and region-dependent contribution of stromal fibroblasts to fibrosis following traumatic injury in mice","authors":"Daniel Holl, Wing Fung Hau, Anais Julien, Shervin Banitalebi, Jannis Kalkitsas, Soniya Savant, Enric Llorens-Bobadilla, Yann Herault, Guillaume Pavlovic, Mahmood Amiry-Moghaddam, David Oliveira Dias, Christian Göritz","doi":"10.1038/s41593-024-01678-4","DOIUrl":"10.1038/s41593-024-01678-4","url":null,"abstract":"Fibrotic scar tissue formation occurs in humans and mice. The fibrotic scar impairs tissue regeneration and functional recovery. However, the origin of scar-forming fibroblasts is unclear. Here, we show that stromal fibroblasts forming the fibrotic scar derive from two populations of perivascular cells after spinal cord injury (SCI) in adult mice of both sexes. We anatomically and transcriptionally identify the two cell populations as pericytes and perivascular fibroblasts. Fibroblasts and pericytes are enriched in the white and gray matter regions of the spinal cord, respectively. Both cell populations are recruited in response to SCI and inflammation. However, their contribution to fibrotic scar tissue depends on the location of the lesion. Upon injury, pericytes and perivascular fibroblasts become activated and transcriptionally converge on the generation of stromal myofibroblasts. Our results show that pericytes and perivascular fibroblasts contribute to the fibrotic scar in a region-dependent manner. The origin and composition of stromal fibroblasts in the fibrotic CNS scar are unclear. Here, the authors demonstrate that pericytes and perivascular fibroblasts contribute to fibrotic scarring following spinal cord injury in mice in a region-dependent manner.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01678-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141287259","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}
Pub Date : 2024-06-07DOI: 10.1038/s41593-024-01675-7
Kristopher T. Jensen, Guillaume Hennequin, Marcelo G. Mattar
When faced with a novel situation, people often spend substantial periods of time contemplating possible futures. For such planning to be rational, the benefits to behavior must compensate for the time spent thinking. Here, we capture these features of behavior by developing a neural network model where planning itself is controlled by the prefrontal cortex. This model consists of a meta-reinforcement learning agent augmented with the ability to plan by sampling imagined action sequences from its own policy, which we call ‘rollouts’. In a spatial navigation task, the agent learns to plan when it is beneficial, which provides a normative explanation for empirical variability in human thinking times. Additionally, the patterns of policy rollouts used by the artificial agent closely resemble patterns of rodent hippocampal replays. Our work provides a theory of how the brain could implement planning through prefrontal–hippocampal interactions, where hippocampal replays are triggered by—and adaptively affect—prefrontal dynamics. Rational planning requires time spent thinking. Here, the authors propose a model of planning where a frontal network triggers hippocampal replay, integrating the replayed trajectory in its recurrent dynamics to improve decisions.
{"title":"A recurrent network model of planning explains hippocampal replay and human behavior","authors":"Kristopher T. Jensen, Guillaume Hennequin, Marcelo G. Mattar","doi":"10.1038/s41593-024-01675-7","DOIUrl":"10.1038/s41593-024-01675-7","url":null,"abstract":"When faced with a novel situation, people often spend substantial periods of time contemplating possible futures. For such planning to be rational, the benefits to behavior must compensate for the time spent thinking. Here, we capture these features of behavior by developing a neural network model where planning itself is controlled by the prefrontal cortex. This model consists of a meta-reinforcement learning agent augmented with the ability to plan by sampling imagined action sequences from its own policy, which we call ‘rollouts’. In a spatial navigation task, the agent learns to plan when it is beneficial, which provides a normative explanation for empirical variability in human thinking times. Additionally, the patterns of policy rollouts used by the artificial agent closely resemble patterns of rodent hippocampal replays. Our work provides a theory of how the brain could implement planning through prefrontal–hippocampal interactions, where hippocampal replays are triggered by—and adaptively affect—prefrontal dynamics. Rational planning requires time spent thinking. Here, the authors propose a model of planning where a frontal network triggers hippocampal replay, integrating the replayed trajectory in its recurrent dynamics to improve decisions.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01675-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141287238","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}
Pub Date : 2024-06-07DOI: 10.1038/s41593-024-01665-9
Vittorio Gallo, Panagiotis Kratimenos
After spinal cord injury, stromal fibroblasts originate from pericytes and perivascular fibroblasts, with pericytes more prevalent in gray matter and fibroblasts in white matter. Holl et al. show that both cell types respond to injury and inflammation, are activated, and transcriptionally converge on scar formation after injury, paving the way for therapeutic possibilities.
{"title":"Each scar whispers a story","authors":"Vittorio Gallo, Panagiotis Kratimenos","doi":"10.1038/s41593-024-01665-9","DOIUrl":"10.1038/s41593-024-01665-9","url":null,"abstract":"After spinal cord injury, stromal fibroblasts originate from pericytes and perivascular fibroblasts, with pericytes more prevalent in gray matter and fibroblasts in white matter. Holl et al. show that both cell types respond to injury and inflammation, are activated, and transcriptionally converge on scar formation after injury, paving the way for therapeutic possibilities.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141287143","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}
Pub Date : 2024-06-07DOI: 10.1038/s41593-024-01688-2
Shari Wiseman
{"title":"One cubic millimeter of human cortex, solved","authors":"Shari Wiseman","doi":"10.1038/s41593-024-01688-2","DOIUrl":"10.1038/s41593-024-01688-2","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":25.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141287052","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}
Pub Date : 2024-06-07DOI: 10.1038/s41593-024-01686-4
George Andrew S. Inglis
{"title":"Sleeping with the zebrafishes","authors":"George Andrew S. Inglis","doi":"10.1038/s41593-024-01686-4","DOIUrl":"10.1038/s41593-024-01686-4","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":25.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141287242","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}
Pub Date : 2024-06-07DOI: 10.1038/s41593-024-01660-0
George Inglis
To celebrate Pride month in the USA, Nature Neuroscience is having conversations with LGBTQIA+ scientists across multiple career stages to discuss their personal and professional experiences in research. In this Q&A, we are talking to Laura Huckins, an associate professor at Yale University School of Medicine, New Haven, USA. Huckins’ research focuses primarily on the genetics of eating disorders and post-traumatic stress disorder, as well as the development of statistical and multi-omic methods for use in genome-wide association studies (GWASs).
{"title":"In conversation with Laura Huckins","authors":"George Inglis","doi":"10.1038/s41593-024-01660-0","DOIUrl":"10.1038/s41593-024-01660-0","url":null,"abstract":"To celebrate Pride month in the USA, Nature Neuroscience is having conversations with LGBTQIA+ scientists across multiple career stages to discuss their personal and professional experiences in research. In this Q&A, we are talking to Laura Huckins, an associate professor at Yale University School of Medicine, New Haven, USA. Huckins’ research focuses primarily on the genetics of eating disorders and post-traumatic stress disorder, as well as the development of statistical and multi-omic methods for use in genome-wide association studies (GWASs).","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":25.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141287150","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}
Pub Date : 2024-06-04DOI: 10.1038/s41593-024-01672-w
Keertana Ganesan, Abigail Thompson, Claire R. Smid, Roser Cañigueral, Yongjing Li, Grace Revill, Vanessa Puetz, Boris C. Bernhardt, Nico U. F. Dosenbach, Rogier Kievit, Nikolaus Steinbeis
Cognitive control is required to organize thoughts and actions and is critical for the pursuit of long-term goals. Childhood cognitive control relates to other domains of cognitive functioning and predicts later-life success and well-being. In this study, we used a randomized controlled trial to test whether cognitive control can be improved through a pre-registered 8-week intervention in 235 children aged 6–13 years targeting response inhibition and whether this leads to changes in multiple behavioral and neural outcomes compared to a response speed training. We show long-lasting improvements of closely related measures of cognitive control at the 1-year follow-up; however, training had no impact on any behavioral outcomes (decision-making, academic achievement, mental health, fluid reasoning and creativity) or neural outcomes (task-dependent and intrinsic brain function and gray and white matter structure). Bayesian analyses provide strong evidence of absent training effects. We conclude that targeted training of response inhibition does little to change children’s brains or their behavior. Cognitive control is important for later-life success and is often targeted for interventions. Here the authors show that response inhibition training in a large sample of children over 8 weeks did not change their brains or behavior in the short or long term.
{"title":"Cognitive control training with domain-general response inhibition does not change children’s brains or behavior","authors":"Keertana Ganesan, Abigail Thompson, Claire R. Smid, Roser Cañigueral, Yongjing Li, Grace Revill, Vanessa Puetz, Boris C. Bernhardt, Nico U. F. Dosenbach, Rogier Kievit, Nikolaus Steinbeis","doi":"10.1038/s41593-024-01672-w","DOIUrl":"10.1038/s41593-024-01672-w","url":null,"abstract":"Cognitive control is required to organize thoughts and actions and is critical for the pursuit of long-term goals. Childhood cognitive control relates to other domains of cognitive functioning and predicts later-life success and well-being. In this study, we used a randomized controlled trial to test whether cognitive control can be improved through a pre-registered 8-week intervention in 235 children aged 6–13 years targeting response inhibition and whether this leads to changes in multiple behavioral and neural outcomes compared to a response speed training. We show long-lasting improvements of closely related measures of cognitive control at the 1-year follow-up; however, training had no impact on any behavioral outcomes (decision-making, academic achievement, mental health, fluid reasoning and creativity) or neural outcomes (task-dependent and intrinsic brain function and gray and white matter structure). Bayesian analyses provide strong evidence of absent training effects. We conclude that targeted training of response inhibition does little to change children’s brains or their behavior. Cognitive control is important for later-life success and is often targeted for interventions. Here the authors show that response inhibition training in a large sample of children over 8 weeks did not change their brains or behavior in the short or long term.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01672-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141246262","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}
Pub Date : 2024-06-04DOI: 10.1038/s41593-024-01693-5
Michael A. Jensen, Harvey Huang, Gabriela Ojeda Valencia, Bryan T. Klassen, Max A. van den Boom, Timothy J. Kaufmann, Gerwin Schalk, Peter Brunner, Gregory A. Worrell, Dora Hermes, Kai J. Miller
{"title":"Author Correction: A motor association area in the depths of the central sulcus","authors":"Michael A. Jensen, Harvey Huang, Gabriela Ojeda Valencia, Bryan T. Klassen, Max A. van den Boom, Timothy J. Kaufmann, Gerwin Schalk, Peter Brunner, Gregory A. Worrell, Dora Hermes, Kai J. Miller","doi":"10.1038/s41593-024-01693-5","DOIUrl":"10.1038/s41593-024-01693-5","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11239484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248293","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}
Pub Date : 2024-06-03DOI: 10.1038/s41593-024-01667-7
Specifically mutating the neurofibromatosis type 1 gene (NF1) in oligodendrocyte precursor cells (OPCs) impairs their adaptive response to neuronal activity and their differentiation into mature oligodendrocytes, as well as promoting focal regions of OPC hyperdensity. These defects delay oligodendroglial development and impede adaptive oligodendrogenesis, which are important for motor learning.
{"title":"Glial plasticity dysregulation contributes to learning impairments in the neurogenetic disorder NF1","authors":"","doi":"10.1038/s41593-024-01667-7","DOIUrl":"10.1038/s41593-024-01667-7","url":null,"abstract":"Specifically mutating the neurofibromatosis type 1 gene (NF1) in oligodendrocyte precursor cells (OPCs) impairs their adaptive response to neuronal activity and their differentiation into mature oligodendrocytes, as well as promoting focal regions of OPC hyperdensity. These defects delay oligodendroglial development and impede adaptive oligodendrogenesis, which are important for motor learning.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141235971","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}
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