Charles A. Nelson, Eileen F. Sullivan, Viviane Valdes
{"title":"Early adversity alters brain architecture and increases susceptibility to mental health disorders","authors":"Charles A. Nelson, Eileen F. Sullivan, Viviane Valdes","doi":"10.1038/s41583-025-00948-9","DOIUrl":"https://doi.org/10.1038/s41583-025-00948-9","url":null,"abstract":"<p>Each year, millions of children around the world are exposed to a host of adverse experiences early in life. These include various forms of maltreatment, growing up in unsafe neighbourhoods, and witnessing intimate partner violence. These experiences exact a toll on the brain development and mental health of children. In this Review, we attempt to explain how brain architecture and circuitry are affected by exposure to such early adversity, which in turn increases susceptibility to mental health disorders later in life. We begin defining what we mean by early adversity and then summarize the experience-dependent nature of postnatal brain development. Within this context, we discuss times in development when the brain is particularly receptive to experience (critical periods) and, thus, is more vulnerable to adverse experiences. Drawing from studies with both rodent and non-human primate models and neuroimaging research with humans, we next discuss how the circuitry of the brain is affected by early-life adversity, with a focus on the subsequent effects upon neural network development. We then review the mental health consequences of adverse experiences in early life across mental health disorders and within specific dimensions of psychopathology. We conclude by offering a conceptual model of the pathway that links exposure to adversity early in life to these mental health outcomes later in life, and we provide suggestions for future research.</p>","PeriodicalId":19082,"journal":{"name":"Nature Reviews Neuroscience","volume":"7 1","pages":""},"PeriodicalIF":34.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694064","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}
Fernando E. Rosas, Andrea I. Luppi, Pedro A. M. Mediano, Morten L. Kringelbach, Luiz Pessoa, Federico Turkheimer
{"title":"Top-down and bottom-up neuroscience: overcoming the clash of research cultures","authors":"Fernando E. Rosas, Andrea I. Luppi, Pedro A. M. Mediano, Morten L. Kringelbach, Luiz Pessoa, Federico Turkheimer","doi":"10.1038/s41583-025-00946-x","DOIUrl":"https://doi.org/10.1038/s41583-025-00946-x","url":null,"abstract":"As scientists, we want solid answers, but we also want to answer questions that matter. Yet, the brain’s complexity forces trade-offs between these desiderata, bringing about two distinct research approaches in neuroscience that we describe as ‘top-down’ and ‘bottom-up’. Recognizing the validity of both approaches dispels misunderstandings and unnecessary tension and promotes constructive interactions.","PeriodicalId":19082,"journal":{"name":"Nature Reviews Neuroscience","volume":"13 1","pages":""},"PeriodicalIF":34.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677247","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}
{"title":"Reward encoded relative to experience","authors":"Jake Rogers","doi":"10.1038/s41583-025-00951-0","DOIUrl":"https://doi.org/10.1038/s41583-025-00951-0","url":null,"abstract":"Population activity of hippocampal place cells in mice flexibly encodes reward-relative representations of experience, which can amplify behaviorally relevant sequences of events in memory.","PeriodicalId":19082,"journal":{"name":"Nature Reviews Neuroscience","volume":"37 1","pages":""},"PeriodicalIF":34.7,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652571","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}
{"title":"Towards single-cell-resolution global maps of mammalian brains","authors":"Chengyu T. Li, Wu Wei","doi":"10.1038/s41583-025-00949-8","DOIUrl":"https://doi.org/10.1038/s41583-025-00949-8","url":null,"abstract":"Brain cell atlases are revolutionizing neuroscience by using single-cell and spatial genomics to reveal the brain’s cellular diversity across development, function and disease. Fully realizing the potential of these atlases requires continued technology improvement, multimodal data integration and strategies to address ethical challenges, paving the way for transformative discoveries in neuroscience and clinical applications.","PeriodicalId":19082,"journal":{"name":"Nature Reviews Neuroscience","volume":"2 1","pages":""},"PeriodicalIF":34.7,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640384","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}
Tongtong Wang, Avedis Tufenkjian, Olujimi A. Ajijola, Yuki Oka
{"title":"Molecular and functional diversity of the autonomic nervous system","authors":"Tongtong Wang, Avedis Tufenkjian, Olujimi A. Ajijola, Yuki Oka","doi":"10.1038/s41583-025-00941-2","DOIUrl":"https://doi.org/10.1038/s41583-025-00941-2","url":null,"abstract":"<p>The autonomic nervous system (ANS) plays a pivotal role in regulating organ functions through descending brain-to-body signalling. The pathways involved are broadly categorized into two major branches: the sympathetic nervous system, which mediates ‘fight or flight’ responses, and the parasympathetic nervous system, which governs ‘rest and digest’ functions. Historically, the ANS was considered to mediate simple motor functions with limited neurochemical diversity. However, recent advances in neurotechnology have shown that brain-to-body communication is more complex and dynamic than previously appreciated. This review synthesizes current knowledge about the molecular, anatomical and functional diversity of autonomic motor neurons. Here we present a comparative analysis of the cellular architecture of the ANS and the suggested roles of distinct neuron populations. Additionally, we explore the emerging view that the ANS interacts with diverse systems involving metabolism, immunology and ageing, which extends its role beyond simple brain–organ modulation. Finally, we emphasize the need for cell-type-specific and longitudinal studies of the ANS to uncover novel mechanisms underlying body–brain interactions and to identify new translational opportunities for therapeutic interventions.</p>","PeriodicalId":19082,"journal":{"name":"Nature Reviews Neuroscience","volume":"77 1","pages":""},"PeriodicalIF":34.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546985","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}
{"title":"Repulsion in the human hippocampus is linked to internal beliefs","authors":"Caroline Barranco","doi":"10.1038/s41583-025-00947-w","DOIUrl":"https://doi.org/10.1038/s41583-025-00947-w","url":null,"abstract":"In humans, repulsion effects occur in specific subfields of the hippocampus and are associated with the presence of distinct internal beliefs about highly similar visual inputs.","PeriodicalId":19082,"journal":{"name":"Nature Reviews Neuroscience","volume":"26 1","pages":""},"PeriodicalIF":34.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520840","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}
{"title":"A new myeloid cell migration route","authors":"Sian Lewis","doi":"10.1038/s41583-025-00944-z","DOIUrl":"https://doi.org/10.1038/s41583-025-00944-z","url":null,"abstract":"In a mouse model of multiple sclerosis, trafficking into the brain parenchyma of the peripheral myeloid cells that are involved in the symptomaptology is shown to occur predominantly via the velum interpositum, a leptomeningeal tract that runs underneath the hippocampal formation.","PeriodicalId":19082,"journal":{"name":"Nature Reviews Neuroscience","volume":"648 1","pages":""},"PeriodicalIF":34.7,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488733","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}
{"title":"A reality check","authors":"Katherine Whalley","doi":"10.1038/s41583-025-00942-1","DOIUrl":"https://doi.org/10.1038/s41583-025-00942-1","url":null,"abstract":"This study reveals a mechanism through which the brain can determine whether perceptual signals reflect external reality or arise from imagination.","PeriodicalId":19082,"journal":{"name":"Nature Reviews Neuroscience","volume":"17 1","pages":""},"PeriodicalIF":34.7,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488732","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}
{"title":"Rethinking excitation/inhibition balance in the human brain","authors":"Roi Cohen Kadosh","doi":"10.1038/s41583-025-00943-0","DOIUrl":"https://doi.org/10.1038/s41583-025-00943-0","url":null,"abstract":"The balance between neural excitation (E) and inhibition (I) shapes cognition, development and brain-based disorders. Electroencephalography and magnetic resonance spectroscopy allow non-invasive quantification of the E/I ratio but yield discrepancies that challenge their use in this context. Addressing these differences is essential for advancing biomarkers and brain-based therapies.","PeriodicalId":19082,"journal":{"name":"Nature Reviews Neuroscience","volume":"18 1","pages":""},"PeriodicalIF":34.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144341269","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}
Robert Prevedel, Júlia Ferrer Ortas, Jason N. D. Kerr, Jack Waters, Michael O. Breckwoldt, Benjamin Deneen, Michelle Monje, Stella J. Soyka, Varun Venkataramani
{"title":"Three-photon microscopy: an emerging technique for deep intravital brain imaging","authors":"Robert Prevedel, Júlia Ferrer Ortas, Jason N. D. Kerr, Jack Waters, Michael O. Breckwoldt, Benjamin Deneen, Michelle Monje, Stella J. Soyka, Varun Venkataramani","doi":"10.1038/s41583-025-00937-y","DOIUrl":"https://doi.org/10.1038/s41583-025-00937-y","url":null,"abstract":"<p>Understanding brain function and pathology requires observation of cellular dynamics within intact neural circuits. Although two-photon microscopy revolutionized mammalian in vivo brain imaging, its limitation to upper cortical layers has restricted access to many important brain regions. Three-photon microscopy overcomes this constraint, enabling minimally invasive yet high-resolution visualization of the deep cortical and subcortical structures that are crucial for higher-order brain functions. This emerging technology opens new avenues for investigating fundamental aspects of neuroscience, from circuit dynamics to disease mechanisms. Here, we examine how three-photon microscopy has started to transform our ability to investigate neural circuits, glial biology, and oncological and neuroimmune interactions in previously inaccessible brain regions, primarily in the mouse, but also in other model organisms. We discuss current technical challenges, recent innovations and future applications that promise to bring us greater understanding of the living brain.</p>","PeriodicalId":19082,"journal":{"name":"Nature Reviews Neuroscience","volume":"46 1","pages":""},"PeriodicalIF":34.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329049","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}