{"title":"Opening the gate to regeneration","authors":"Sian Lewis","doi":"10.1038/s41583-024-00875-1","DOIUrl":"10.1038/s41583-024-00875-1","url":null,"abstract":"After injury, regeneration of retinal ganglion cells and reconnection to their original target — the suprachiasmatic nucleus —is achieved by manipulating guidance cues, leading to the formation of a functional circuit that supports functional recovery.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"25 12","pages":"758-758"},"PeriodicalIF":28.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519256","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":"Fly connectome over the wire","authors":"Jake Rogers","doi":"10.1038/s41583-024-00879-x","DOIUrl":"10.1038/s41583-024-00879-x","url":null,"abstract":"A series of papers provide an overview of the adult Drosophila melanogaster whole-brain connectome and how the resulting resource allows for more sophisticated approaches to investigate computations in the fly brain.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"25 12","pages":"757-757"},"PeriodicalIF":28.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519258","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}
Sanju Koirala, Gracie Grimsrud, Michael A. Mooney, Bart Larsen, Eric Feczko, Jed T. Elison, Steven M. Nelson, Joel T. Nigg, Brenden Tervo-Clemmens, Damien A. Fair
{"title":"Neurobiology of attention-deficit hyperactivity disorder: historical challenges and emerging frontiers","authors":"Sanju Koirala, Gracie Grimsrud, Michael A. Mooney, Bart Larsen, Eric Feczko, Jed T. Elison, Steven M. Nelson, Joel T. Nigg, Brenden Tervo-Clemmens, Damien A. Fair","doi":"10.1038/s41583-024-00869-z","DOIUrl":"10.1038/s41583-024-00869-z","url":null,"abstract":"Extensive investigations spanning multiple levels of inquiry, from genetic to behavioural studies, have sought to unravel the mechanistic foundations of attention-deficit hyperactivity disorder (ADHD), with the aspiration of developing efficacious treatments for this condition. Despite these efforts, the pathogenesis of ADHD remains elusive. In this Review, we reflect on what has been learned about ADHD while also providing a framework that may serve as a roadmap for future investigations. We emphasize that ADHD is a highly heterogeneous disorder with multiple aetiologies that necessitates a multifactorial dimensional phenotype, rather than a fixed dichotomous conceptualization. We highlight new findings that suggest a more brain-wide, ‘global’ view of the disorder, rather than the traditional localizationist framework, which asserts that a limited set of brain regions or networks underlie ADHD. Last, we underscore how underpowered studies that have aimed to associate neurobiology with ADHD phenotypes have long precluded the field from making progress. However, a new age of ADHD research with refined phenotypes, advanced methods, creative study designs and adequately powered investigations is beginning to put the field on a good footing. Indeed, the field is at a promising juncture to advance the neurobiological understanding of ADHD and fulfil the promise of clinical utility. Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition that is poorly understood at a neurobiological level. In this Review, Fair and colleagues examine studies of ADHD neurobiology and provide a perspective on how the field may move forward.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"25 12","pages":"759-775"},"PeriodicalIF":28.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488462","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":"Social and emotional learning in the cerebellum","authors":"Frank Van Overwalle","doi":"10.1038/s41583-024-00871-5","DOIUrl":"10.1038/s41583-024-00871-5","url":null,"abstract":"The posterior cerebellum has a critical role in human social and emotional learning. Three systems and related neural networks support this cerebellar function: a biological action observation system as part of an extended sensorimotor integration network, a mentalizing system for understanding a person’s mental and emotional state subserved by a mentalizing network, and a limbic network supporting core emotional (dis)pleasure and arousal processes. In this Review, I describe how these systems and networks support social and emotional learning via functional reciprocal connections initiating and terminating in the posterior cerebellum and cerebral neocortex. It is hypothesized that a major function of the posterior cerebellum is to identify and encode temporal sequences of events, which might help to fine-tune and automatize social and emotional learning. I discuss research using neuroimaging and non-invasive stimulation that provides converging evidence for this hypothesized function of cerebellar sequencing, but also other potential functional accounts of the posterior cerebellum’s role in these social and emotional processes. The cerebellum’s canonical role in learning is expanding beyond movement coordination. In this Review, Van Overwalle details the systems and networks facilitating the cerebellum’s role in human social and emotional learning and discusses whether cerebellar temporal sequencing might account for this functionality.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"25 12","pages":"776-791"},"PeriodicalIF":28.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452397","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}
Shailendra Segobin, Roy A. M. Haast, Vinod Jangir Kumar, Annalisa Lella, Anneke Alkemade, Meritxell Bach Cuadra, Emmanuel J. Barbeau, Olivier Felician, Giulio Pergola, Anne-Lise Pitel, Manojkumar Saranathan, Thomas Tourdias, Michael Hornberger
{"title":"A roadmap towards standardized neuroimaging approaches for human thalamic nuclei","authors":"Shailendra Segobin, Roy A. M. Haast, Vinod Jangir Kumar, Annalisa Lella, Anneke Alkemade, Meritxell Bach Cuadra, Emmanuel J. Barbeau, Olivier Felician, Giulio Pergola, Anne-Lise Pitel, Manojkumar Saranathan, Thomas Tourdias, Michael Hornberger","doi":"10.1038/s41583-024-00867-1","DOIUrl":"10.1038/s41583-024-00867-1","url":null,"abstract":"The thalamus has a key role in mediating cortical–subcortical interactions but is often neglected in neuroimaging studies, which mostly focus on changes in cortical structure and activity. One of the main reasons for the thalamus being overlooked is that the delineation of individual thalamic nuclei via neuroimaging remains controversial. Indeed, neuroimaging atlases vary substantially regarding which thalamic nuclei are included and how their delineations were established. Here, we review current and emerging methods for thalamic nuclei segmentation in neuroimaging data and consider the limitations of existing techniques in terms of their research and clinical applicability. We address these challenges by proposing a roadmap to improve thalamic nuclei segmentation in human neuroimaging and, in turn, harmonize research approaches and advance clinical applications. We believe that a collective effort is required to achieve this. We hope that this will ultimately lead to the thalamic nuclei being regarded as key brain regions in their own right and not (as often currently assumed) as simply a gateway between cortical and subcortical regions. The human thalamus comprises multiple nuclei with distinct connectivity patterns and anatomical features; however, current neuroimaging approaches have a limited capacity to delinate individual thalamic nuclei. Segobin and colleagues outline the challenges that this presents to our understanding of the function of these nuclei and propose a roadmap for the future of thalamic neuroimaging.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"25 12","pages":"792-808"},"PeriodicalIF":28.7,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440825","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}
Dorian Battivelli, Zhengxiao Fan, Hailan Hu, Cornelius T. Gross
{"title":"How can ethology inform the neuroscience of fear, aggression and dominance?","authors":"Dorian Battivelli, Zhengxiao Fan, Hailan Hu, Cornelius T. Gross","doi":"10.1038/s41583-024-00858-2","DOIUrl":"10.1038/s41583-024-00858-2","url":null,"abstract":"The study of behaviour is dominated by two approaches. On the one hand, ethologists aim to understand how behaviour promotes adaptation to natural contexts. On the other, neuroscientists aim to understand the molecular, cellular, circuit and psychological origins of behaviour. These two complementary approaches must be combined to arrive at a full understanding of behaviour in its natural setting. However, methodological limitations have restricted most neuroscientific research to the study of how discrete sensory stimuli elicit simple behavioural responses under controlled laboratory conditions that are only distantly related to those encountered in real life. Fortunately, the recent advent of neural monitoring and manipulation tools adapted for use in freely behaving animals has enabled neuroscientists to incorporate naturalistic behaviours into their studies and to begin to consider ethological questions. Here, we examine the promises and pitfalls of this trend by describing how investigations of rodent fear, aggression and dominance behaviours are changing to take advantage of an ethological appreciation of behaviour. We lay out current impediments to this approach and propose a framework for the evolution of the field that will allow us to take maximal advantage of an ethological approach to neuroscience and to increase its relevance for understanding human behaviour. Advances in tools available to monitor and manipulate neural activity in freely moving animals can enable the investigation of naturalistic behaviours. In this Perspective, Gross and colleagues outline the challenges that neuroscientists face when incorporating ethological context into studies of fear, aggression and dominance and provide suggestions to overcome these barriers.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"25 12","pages":"809-819"},"PeriodicalIF":28.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431268","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}
Matthew L. Russo, André M. M. Sousa, Anita Bhattacharyya
{"title":"Consequences of trisomy 21 for brain development in Down syndrome","authors":"Matthew L. Russo, André M. M. Sousa, Anita Bhattacharyya","doi":"10.1038/s41583-024-00866-2","DOIUrl":"10.1038/s41583-024-00866-2","url":null,"abstract":"The appearance of cognitive deficits and altered brain morphology in newborns with Down syndrome (DS) suggests that these features are driven by disruptions at the earliest stages of brain development. Despite its high prevalence and extensively characterized cognitive phenotypes, relatively little is known about the cellular and molecular mechanisms that drive the changes seen in DS. Recent technical advances, such as single-cell omics and the development of induced pluripotent stem cell (iPSC) models of DS, now enable in-depth analyses of the biochemical and molecular drivers of altered brain development in DS. Here, we review the current state of knowledge on brain development in DS, focusing primarily on data from human post-mortem brain tissue. We explore the biological mechanisms that have been proposed to lead to intellectual disability in DS, assess the extent to which data from studies using iPSC models supports these hypotheses, and identify current gaps in the field. Trisomy 21, the genetic cause of Down syndrome, is associated with both cognitive deficits and altered brain structure. Here, Anita Bhattacharyya and colleagues discuss our current understanding of the neurodevelopmental mechanisms that are disrupted in Down syndrome and that underlie these changes.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"25 11","pages":"740-755"},"PeriodicalIF":28.7,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384215","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":"RNA granules in flux: dynamics to balance physiology and pathology","authors":"Michael A. Kiebler, Karl E. Bauer","doi":"10.1038/s41583-024-00859-1","DOIUrl":"10.1038/s41583-024-00859-1","url":null,"abstract":"The life cycle of an mRNA is a complex process that is tightly regulated by interactions between the mRNA and RNA-binding proteins, forming molecular machines known as RNA granules. Various types of these membrane-less organelles form inside cells, including neurons, and contribute critically to various physiological processes. RNA granules are constantly in flux, change dynamically and adapt to their local environment, depending on their intracellular localization. The discovery that RNA condensates can form by liquid–liquid phase separation expanded our understanding of how compartments may be generated in the cell. Since then, a plethora of new functions have been proposed for distinct condensates in cells that await their validation in vivo. The finding that dysregulation of RNA granules (for example, stress granules) is likely to affect neurodevelopmental and neurodegenerative diseases further boosted interest in this topic. RNA granules have various physiological functions in neurons and in the brain that we would like to focus on. We outline examples of state-of-the-art experiments including timelapse microscopy in neurons to unravel the precise functions of various types of RNA granule. Finally, we distinguish physiologically occurring RNA condensation from aberrant aggregation, induced by artificial RNA overexpression, and present visual examples to discriminate both forms in neurons. The physiological dynamics of the molecular machines known as RNA granules have broad implications for neuronal function. In this Review, Kiebler and Bauer discuss the many open questions remaining and highlight recent research, experimental caveats and novel approaches.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"25 11","pages":"711-725"},"PeriodicalIF":28.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374141","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}