Pub Date : 2025-07-03DOI: 10.1038/s41583-025-00941-2
Tongtong Wang, Avedis Tufenkjian, Olujimi A. Ajijola, Yuki Oka
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. The autonomic nervous system has long been viewed as a simple motor system in brain-to-body signalling. In this review, Wang and colleagues highlight diversity within autonomic neurons and their dynamic roles across physiological systems and disease contexts.
{"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":"10.1038/s41583-025-00941-2","url":null,"abstract":"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. The autonomic nervous system has long been viewed as a simple motor system in brain-to-body signalling. In this review, Wang and colleagues highlight diversity within autonomic neurons and their dynamic roles across physiological systems and disease contexts.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"26 10","pages":"607-622"},"PeriodicalIF":26.7,"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}
Pub Date : 2025-07-01DOI: 10.1038/s41583-025-00947-w
Caroline Barranco
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.
在人类中，排斥效应发生在海马体的特定子区，并与对高度相似的视觉输入的不同内部信念的存在有关。
{"title":"Repulsion in the human hippocampus is linked to internal beliefs","authors":"Caroline Barranco","doi":"10.1038/s41583-025-00947-w","DOIUrl":"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":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"26 8","pages":"453-453"},"PeriodicalIF":26.7,"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}
Pub Date : 2025-06-26DOI: 10.1038/s41583-025-00944-z
Sian Lewis
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.
{"title":"A new myeloid cell migration route","authors":"Sian Lewis","doi":"10.1038/s41583-025-00944-z","DOIUrl":"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":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"26 8","pages":"454-454"},"PeriodicalIF":26.7,"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}
Pub Date : 2025-06-26DOI: 10.1038/s41583-025-00942-1
Katherine Whalley
This study reveals a mechanism through which the brain can determine whether perceptual signals reflect external reality or arise from imagination.
这项研究揭示了一种机制，通过这种机制，大脑可以确定感知信号是反映外部现实还是来自想象。
{"title":"A reality check","authors":"Katherine Whalley","doi":"10.1038/s41583-025-00942-1","DOIUrl":"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":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"26 8","pages":"455-455"},"PeriodicalIF":26.7,"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}
Pub Date : 2025-06-23DOI: 10.1038/s41583-025-00943-0
Roi Cohen Kadosh
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.
{"title":"Rethinking excitation/inhibition balance in the human brain","authors":"Roi Cohen Kadosh","doi":"10.1038/s41583-025-00943-0","DOIUrl":"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":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"26 8","pages":"451-452"},"PeriodicalIF":26.7,"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}
Pub Date : 2025-06-20DOI: 10.1038/s41583-025-00937-y
Robert Prevedel, Júlia Ferrer Ortas, Jason N. D. Kerr, Jack Waters, Michael O. Breckwoldt, Benjamin Deneen, Michelle Monje, Stella J. Soyka, Varun Venkataramani
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. Optical microscopy allows neural cells to be studied in the intact brain, but imaging deep neural tissue presents substantial challenges. Prevedel and colleagues outline the principles of three-photon microscopy, highlighting its advantages for deep tissue imaging and its applications in neuroscience.
{"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":"10.1038/s41583-025-00937-y","url":null,"abstract":"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. Optical microscopy allows neural cells to be studied in the intact brain, but imaging deep neural tissue presents substantial challenges. Prevedel and colleagues outline the principles of three-photon microscopy, highlighting its advantages for deep tissue imaging and its applications in neuroscience.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"26 9","pages":"521-537"},"PeriodicalIF":26.7,"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}
Pub Date : 2025-06-20DOI: 10.1038/s41583-025-00940-3
Claire J. Foldi, Kristi R. Griffiths
Despite their prevalence, eating disorders (EDs) are under-researched and often misunderstood. A recent focus of research on the biological underpinnings of EDs has helped to reframe our understanding of their origins, but there remain a lack of effective treatment options, high rates of relapse and, unfortunately, high mortality and morbidity. In this Review, we highlight the many facets of normal and pathological feeding behaviour and body weight regulation and suggest that these provide a framework with which to develop integrative methods to study, and ultimately treat, EDs. We propose that a better understanding of the biological causes of ED, and their crucial interactions with psychological and environmental factors, is necessary to progress the field. This can be achieved through a combination of preclinical and clinical investigations, which provide complementary information on these highly complex disorders. In the era of individualized medicine and with the advent of artificial intelligence tools that allow the amalgamation of multimodal data, we hope that a better understanding of the biology of EDs may hold the answer to effectively overcoming the debilitating effects of these conditions. Recent years have seen a growth in our understanding of the biological drivers of eating disorders and their interactions with environmental and psychosocial factors. Foldi and Griffiths consider how interdisciplinary research, dimensional diagnostic approaches and improved animal models may enable the development of more effective treatments for these disorders.
{"title":"Examining the biological causes of eating disorders to inform treatment strategies","authors":"Claire J. Foldi, Kristi R. Griffiths","doi":"10.1038/s41583-025-00940-3","DOIUrl":"10.1038/s41583-025-00940-3","url":null,"abstract":"Despite their prevalence, eating disorders (EDs) are under-researched and often misunderstood. A recent focus of research on the biological underpinnings of EDs has helped to reframe our understanding of their origins, but there remain a lack of effective treatment options, high rates of relapse and, unfortunately, high mortality and morbidity. In this Review, we highlight the many facets of normal and pathological feeding behaviour and body weight regulation and suggest that these provide a framework with which to develop integrative methods to study, and ultimately treat, EDs. We propose that a better understanding of the biological causes of ED, and their crucial interactions with psychological and environmental factors, is necessary to progress the field. This can be achieved through a combination of preclinical and clinical investigations, which provide complementary information on these highly complex disorders. In the era of individualized medicine and with the advent of artificial intelligence tools that allow the amalgamation of multimodal data, we hope that a better understanding of the biology of EDs may hold the answer to effectively overcoming the debilitating effects of these conditions. Recent years have seen a growth in our understanding of the biological drivers of eating disorders and their interactions with environmental and psychosocial factors. Foldi and Griffiths consider how interdisciplinary research, dimensional diagnostic approaches and improved animal models may enable the development of more effective treatments for these disorders.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"26 9","pages":"554-570"},"PeriodicalIF":26.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329068","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 : 2025-06-16DOI: 10.1038/s41583-025-00936-z
Katrina P. Nguyen, Abigail L. Person
The rise of the deep neural network as the workhorse of artificial intelligence has brought increased attention to how network architectures serve specialized functions. The cerebellum, with its largely shallow, feedforward architecture, provides a curious example of such a specialized network. Within the cerebellum, tiny supernumerary granule cells project to a monolayer of giant Purkinje neurons that reweight synaptic inputs under the instructive influence of a unitary synaptic input from climbing fibres. What might this predominantly feedforward organization confer computationally? Here we review evidence for and against the hypothesis that the cerebellum learns basic associative feedforward control policies to speed up motor control and learning. We contrast and link this feedforward control framework with another prominent set of theories proposing that the cerebellum computes internal models. Ultimately, we suggest that the cerebellum may implement control through mechanisms that resemble internal models but involve model-free implicit mappings of high-dimensional sensorimotor contexts to motor output. The cerebellum helps ensure the speed and accuracy of movements, but its precise contributions to movement control are unclear. Nguyen and Person here evaluate evidence for and against feedforward motor control by the cerebellum in light of its well-defined role in a model of associative learning, and reconcile this with theories of internal model-based control.
{"title":"Cerebellar circuit computations for predictive motor control","authors":"Katrina P. Nguyen, Abigail L. Person","doi":"10.1038/s41583-025-00936-z","DOIUrl":"10.1038/s41583-025-00936-z","url":null,"abstract":"The rise of the deep neural network as the workhorse of artificial intelligence has brought increased attention to how network architectures serve specialized functions. The cerebellum, with its largely shallow, feedforward architecture, provides a curious example of such a specialized network. Within the cerebellum, tiny supernumerary granule cells project to a monolayer of giant Purkinje neurons that reweight synaptic inputs under the instructive influence of a unitary synaptic input from climbing fibres. What might this predominantly feedforward organization confer computationally? Here we review evidence for and against the hypothesis that the cerebellum learns basic associative feedforward control policies to speed up motor control and learning. We contrast and link this feedforward control framework with another prominent set of theories proposing that the cerebellum computes internal models. Ultimately, we suggest that the cerebellum may implement control through mechanisms that resemble internal models but involve model-free implicit mappings of high-dimensional sensorimotor contexts to motor output. The cerebellum helps ensure the speed and accuracy of movements, but its precise contributions to movement control are unclear. Nguyen and Person here evaluate evidence for and against feedforward motor control by the cerebellum in light of its well-defined role in a model of associative learning, and reconcile this with theories of internal model-based control.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"26 9","pages":"538-553"},"PeriodicalIF":26.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296059","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 : 2025-06-06DOI: 10.1038/s41583-025-00939-w
Sian Lewis
A polyA-tail-directed RNA sequencing approach that was used to investigate transcriptomic changes in dorsal root ganglia following nerve crush revealed unexpected upregulation of a specific set of B2-SINE transcriptional regulators that facilitate neuronal repair by co-ordinating axon transport and local translation.
{"title":"An intriguing role of repeat-element RNAs in nerve injury repair","authors":"Sian Lewis","doi":"10.1038/s41583-025-00939-w","DOIUrl":"10.1038/s41583-025-00939-w","url":null,"abstract":"A polyA-tail-directed RNA sequencing approach that was used to investigate transcriptomic changes in dorsal root ganglia following nerve crush revealed unexpected upregulation of a specific set of B2-SINE transcriptional regulators that facilitate neuronal repair by co-ordinating axon transport and local translation.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"26 7","pages":"378-378"},"PeriodicalIF":26.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228787","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 : 2025-06-06DOI: 10.1038/s41583-025-00938-x
Jake Rogers
Movement-related dopamine neuronal activity in the tail of the striatum encodes a value-free action prediction error that reinforces state-action associations, biasing mice to repeat past actions.
{"title":"Value-free teaching in action","authors":"Jake Rogers","doi":"10.1038/s41583-025-00938-x","DOIUrl":"10.1038/s41583-025-00938-x","url":null,"abstract":"Movement-related dopamine neuronal activity in the tail of the striatum encodes a value-free action prediction error that reinforces state-action associations, biasing mice to repeat past actions.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"26 7","pages":"377-377"},"PeriodicalIF":26.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228788","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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