Pub Date : 2025-12-31DOI: 10.1038/s41593-025-02142-7
Sergi Roig-Puiggros, Maëlle Guyoton, Dmitrii Suchkov, Aurélien Fortoul, Giulio Matteucci, Sabine Fièvre, Alessandra Panzeri, Nikolaos Molochidis, Francesca Barcellini, Emma Maino, Charlie G. Foucher, Daniel Fuciec, Awais Javed, Esther Klingler, Fiona Francis, Valerio Zerbi, Camilla Bellone, Marat Minlebaev, Sami El-Boustani, Françoise Watrin, Jean-Bernard Manent, Denis Jabaudon
Brain architectures vary widely across species, yet how neuronal positioning constrains the type of circuits that can be made, and their function, remains poorly understood. Here we examine how neuronal position affects molecular identity, connectivity and function by studying Eml1 knockout mice, which exhibit abnormally located (heterotopic) neurons beneath the cortex. Heterotopic neurons maintained their molecular signatures, formed appropriate long-range connections and exhibited coherent electrophysiological properties. They organized into functional sensory-processing centers that mirrored their cortical counterparts, with preserved somatotopic mapping and responsiveness to sensory stimuli. Remarkably, cortical silencing did not impair sensory discrimination, revealing that heterotopic neurons were the main drivers of this function. Hence, equivalent circuits can emerge in different spatial configurations, allowing diverse brain architectures to converge on similar functional outcomes. Even when neocortical neurons form in abnormal locations, they retain their identity and function, revealing that brain circuit formation can be guided by intrinsic developmental programs rather than physical position.
{"title":"Position-independent emergence of neocortical neuron molecular identity, connectivity and function","authors":"Sergi Roig-Puiggros, Maëlle Guyoton, Dmitrii Suchkov, Aurélien Fortoul, Giulio Matteucci, Sabine Fièvre, Alessandra Panzeri, Nikolaos Molochidis, Francesca Barcellini, Emma Maino, Charlie G. Foucher, Daniel Fuciec, Awais Javed, Esther Klingler, Fiona Francis, Valerio Zerbi, Camilla Bellone, Marat Minlebaev, Sami El-Boustani, Françoise Watrin, Jean-Bernard Manent, Denis Jabaudon","doi":"10.1038/s41593-025-02142-7","DOIUrl":"10.1038/s41593-025-02142-7","url":null,"abstract":"Brain architectures vary widely across species, yet how neuronal positioning constrains the type of circuits that can be made, and their function, remains poorly understood. Here we examine how neuronal position affects molecular identity, connectivity and function by studying Eml1 knockout mice, which exhibit abnormally located (heterotopic) neurons beneath the cortex. Heterotopic neurons maintained their molecular signatures, formed appropriate long-range connections and exhibited coherent electrophysiological properties. They organized into functional sensory-processing centers that mirrored their cortical counterparts, with preserved somatotopic mapping and responsiveness to sensory stimuli. Remarkably, cortical silencing did not impair sensory discrimination, revealing that heterotopic neurons were the main drivers of this function. Hence, equivalent circuits can emerge in different spatial configurations, allowing diverse brain architectures to converge on similar functional outcomes. Even when neocortical neurons form in abnormal locations, they retain their identity and function, revealing that brain circuit formation can be guided by intrinsic developmental programs rather than physical position.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"29 2","pages":"315-324"},"PeriodicalIF":20.0,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878693","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 : 2025-12-30DOI: 10.1038/s41593-025-02130-x
Sebastian A. Bruijns, International Brain Laboratory, Kcénia Bougrova, Inês C. Laranjeira, Petrina Y. P. Lau, Guido T. Meijer, Nathaniel J. Miska, Jean-Paul Noel, Alejandro Pan-Vazquez, Noam Roth, Karolina Z. Socha, Anne E. Urai, Peter Dayan
Learning the contingencies of a task is difficult. Individuals learn in an idiosyncratic manner, revising their approach multiple times as they explore and adapt. Quantitative characterization of these learning curves requires a model that can capture both new behaviors and slow changes in existing ones. Here we suggest a dynamic infinite hidden semi-Markov model, whose latent states are associated with specific components of behavior. This model can describe new behaviors by introducing new states and capture more modest adaptations through dynamics in existing states. We tested the model by fitting it to behavioral data of >100 mice learning a contrast-detection task. Although animals showed large interindividual differences while learning this task, most mice progressed through three stages of task understanding, new behavior often arose at session onset, and early response biases did not predict later ones. We thus provide a new tool for comprehensively capturing behavior during learning. Bruijns et al. present a modeling tool that enables the tracking of learning dynamics across subjects to reveal how behaviors emerge and adapt. Applying the tool to a decision-making task in mice uncovers similarities and differences across individuals.
{"title":"Infinite hidden Markov models can dissect the complexities of learning","authors":"Sebastian A. Bruijns, International Brain Laboratory, Kcénia Bougrova, Inês C. Laranjeira, Petrina Y. P. Lau, Guido T. Meijer, Nathaniel J. Miska, Jean-Paul Noel, Alejandro Pan-Vazquez, Noam Roth, Karolina Z. Socha, Anne E. Urai, Peter Dayan","doi":"10.1038/s41593-025-02130-x","DOIUrl":"10.1038/s41593-025-02130-x","url":null,"abstract":"Learning the contingencies of a task is difficult. Individuals learn in an idiosyncratic manner, revising their approach multiple times as they explore and adapt. Quantitative characterization of these learning curves requires a model that can capture both new behaviors and slow changes in existing ones. Here we suggest a dynamic infinite hidden semi-Markov model, whose latent states are associated with specific components of behavior. This model can describe new behaviors by introducing new states and capture more modest adaptations through dynamics in existing states. We tested the model by fitting it to behavioral data of >100 mice learning a contrast-detection task. Although animals showed large interindividual differences while learning this task, most mice progressed through three stages of task understanding, new behavior often arose at session onset, and early response biases did not predict later ones. We thus provide a new tool for comprehensively capturing behavior during learning. Bruijns et al. present a modeling tool that enables the tracking of learning dynamics across subjects to reveal how behaviors emerge and adapt. Applying the tool to a decision-making task in mice uncovers similarities and differences across individuals.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"29 1","pages":"186-194"},"PeriodicalIF":20.0,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41593-025-02130-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145864100","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 : 2025-12-30DOI: 10.1038/s41593-025-02146-3
Micha Hacohen, Adam Levy, Hadas Kaiser, LeeAnne Green Snyder, Alpha Amatya, Brigitta B. Gundersen, John E. Spiro, Ilan Dinstein
The Simons Sleep Project (SSP) is an open-science resource designed to accelerate digital health research into sleep and daily behaviors of autistic children. The SSP contains data from Dreem3 EEG headbands, multi-sensor EmbracePlus smartwatches and Withings’ sleep mats, as well as parent questionnaires and daily sleep diaries. It contains data from >3,600 days and nights collected from 102 children (aged 10–17 years) with idiopathic autism and 98 of their nonautistic siblings, and enables access to whole-exome sequencing for all participants. Here we present the breadth of available harmonized data and show that digital devices have higher accuracy and reliability compared to parent reports. The data show that autistic children have longer sleep-onset latencies than their siblings and longer latencies are associated with behavioral difficulties in all participants, regardless of diagnosis. The results highlight the advantages of using digital devices and demonstrate the opportunities afforded by the SSP to study autism and develop broad digital phenotyping techniques. This paper describes the Simons Sleep Project, an open resource designed to accelerate research into the sleep and daily behaviors of autistic children using synchronized recordings from multiple wearable and nearable devices for >3,600 days and nights.
{"title":"An open science resource for accelerating scalable digital health research in autism and other neurodevelopmental conditions","authors":"Micha Hacohen, Adam Levy, Hadas Kaiser, LeeAnne Green Snyder, Alpha Amatya, Brigitta B. Gundersen, John E. Spiro, Ilan Dinstein","doi":"10.1038/s41593-025-02146-3","DOIUrl":"10.1038/s41593-025-02146-3","url":null,"abstract":"The Simons Sleep Project (SSP) is an open-science resource designed to accelerate digital health research into sleep and daily behaviors of autistic children. The SSP contains data from Dreem3 EEG headbands, multi-sensor EmbracePlus smartwatches and Withings’ sleep mats, as well as parent questionnaires and daily sleep diaries. It contains data from >3,600 days and nights collected from 102 children (aged 10–17 years) with idiopathic autism and 98 of their nonautistic siblings, and enables access to whole-exome sequencing for all participants. Here we present the breadth of available harmonized data and show that digital devices have higher accuracy and reliability compared to parent reports. The data show that autistic children have longer sleep-onset latencies than their siblings and longer latencies are associated with behavioral difficulties in all participants, regardless of diagnosis. The results highlight the advantages of using digital devices and demonstrate the opportunities afforded by the SSP to study autism and develop broad digital phenotyping techniques. This paper describes the Simons Sleep Project, an open resource designed to accelerate research into the sleep and daily behaviors of autistic children using synchronized recordings from multiple wearable and nearable devices for >3,600 days and nights.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"29 2","pages":"467-478"},"PeriodicalIF":20.0,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41593-025-02146-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863993","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 : 2025-12-30DOI: 10.1038/s41593-025-02169-w
Mackenzie Weygandt Mathis
Biological intelligence is inherently adaptive—animals continually adjust their actions in response to environmental feedback. However, creating adaptive artificial intelligence (AI) remains a major challenge. The next frontier is to go beyond traditional AI to develop ‘adaptive intelligence’, defined here as harnessing insights from biological intelligence to build agents that can learn online, generalize and rapidly adapt to changes in their environment. Recent advances in neuroscience offer inspiration through studies that increasingly focus on how animals naturally learn and adapt their models of the world. This Perspective reviews the behavioral and neural foundations of adaptive biological intelligence, examines parallel progress in AI, and explores brain-inspired approaches for building more adaptive algorithms. Adaptive intelligence envisions AI that, like animals, learns online, generalizes and adapts quickly. This Perspective reviews biological foundations, progress in AI and brain-inspired strategies for building flexible and adaptive AI algorithms.
{"title":"Leveraging insights from neuroscience to build adaptive artificial intelligence","authors":"Mackenzie Weygandt Mathis","doi":"10.1038/s41593-025-02169-w","DOIUrl":"10.1038/s41593-025-02169-w","url":null,"abstract":"Biological intelligence is inherently adaptive—animals continually adjust their actions in response to environmental feedback. However, creating adaptive artificial intelligence (AI) remains a major challenge. The next frontier is to go beyond traditional AI to develop ‘adaptive intelligence’, defined here as harnessing insights from biological intelligence to build agents that can learn online, generalize and rapidly adapt to changes in their environment. Recent advances in neuroscience offer inspiration through studies that increasingly focus on how animals naturally learn and adapt their models of the world. This Perspective reviews the behavioral and neural foundations of adaptive biological intelligence, examines parallel progress in AI, and explores brain-inspired approaches for building more adaptive algorithms. Adaptive intelligence envisions AI that, like animals, learns online, generalizes and adapts quickly. This Perspective reviews biological foundations, progress in AI and brain-inspired strategies for building flexible and adaptive AI algorithms.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"29 1","pages":"13-24"},"PeriodicalIF":20.0,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145864093","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 : 2025-12-30DOI: 10.1038/s41593-025-02148-1
Jose Antonio Noriega-Prieto, Rafael Falcón-Moya, Jacob A. Noeker, Ruyi Cai, Unai B. Fundazuri, Abel Eraso-Pichot, Shangxuan Cai, Pavan Guttipatti, Lindsey Belisle, Antonio Rodríguez-Moreno, Mario van der Stelt, Yulong Li, Joseph F. Cheer, Giovanni Marsicano, Paulo Kofuji, Alfonso Araque
The endocannabinoid (eCB) system is involved in many processes in brain function. eCBs depress synaptic transmission by directly activating presynaptic CB1 receptors (CB1Rs), and they indirectly potentiate adjacent synapses by activating astrocytic CB1Rs. In contrast to other neurotransmitter systems, the brain eCB system involves two endogenous ligands, 2-arachidonoylglycerol (2-AG) and anandamide (AEA), and the receptor CB1R. The meaning of this particularity remains unknown. Here we show that 2-AG selectively signals to neurons, eliciting the depression, which is mediated exclusively by neuronal mechanisms. By contrast, AEA signals to astrocytes, inducing lateral synaptic potentiation. Moreover, AEA, but not 2-AG, and astrocyte-mediated signaling are required for hippocampal spike-timing-dependent long-term potentiation. Hence, while 2-AG selectively signals to neurons, AEA specifically signals to astrocytes, evoking contrasting regulatory phenomena of synaptic transmission and plasticity. These results reveal distinct cell-type-specific signaling pathways that involve unique eCBs selectively signaling to either neurons or astrocytes. Distinct endocannabinoids signal to either astrocytes or neurons, evoking contrasting regulation of synaptic function. This works reveals the high degree of complexity of neuronal and astrocytic signaling in brain function.
{"title":"Distinct endocannabinoids specifically signal to astrocytes or neurons in the adult mouse hippocampus","authors":"Jose Antonio Noriega-Prieto, Rafael Falcón-Moya, Jacob A. Noeker, Ruyi Cai, Unai B. Fundazuri, Abel Eraso-Pichot, Shangxuan Cai, Pavan Guttipatti, Lindsey Belisle, Antonio Rodríguez-Moreno, Mario van der Stelt, Yulong Li, Joseph F. Cheer, Giovanni Marsicano, Paulo Kofuji, Alfonso Araque","doi":"10.1038/s41593-025-02148-1","DOIUrl":"10.1038/s41593-025-02148-1","url":null,"abstract":"The endocannabinoid (eCB) system is involved in many processes in brain function. eCBs depress synaptic transmission by directly activating presynaptic CB1 receptors (CB1Rs), and they indirectly potentiate adjacent synapses by activating astrocytic CB1Rs. In contrast to other neurotransmitter systems, the brain eCB system involves two endogenous ligands, 2-arachidonoylglycerol (2-AG) and anandamide (AEA), and the receptor CB1R. The meaning of this particularity remains unknown. Here we show that 2-AG selectively signals to neurons, eliciting the depression, which is mediated exclusively by neuronal mechanisms. By contrast, AEA signals to astrocytes, inducing lateral synaptic potentiation. Moreover, AEA, but not 2-AG, and astrocyte-mediated signaling are required for hippocampal spike-timing-dependent long-term potentiation. Hence, while 2-AG selectively signals to neurons, AEA specifically signals to astrocytes, evoking contrasting regulatory phenomena of synaptic transmission and plasticity. These results reveal distinct cell-type-specific signaling pathways that involve unique eCBs selectively signaling to either neurons or astrocytes. Distinct endocannabinoids signal to either astrocytes or neurons, evoking contrasting regulation of synaptic function. This works reveals the high degree of complexity of neuronal and astrocytic signaling in brain function.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"29 2","pages":"445-454"},"PeriodicalIF":20.0,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145864126","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 : 2025-12-29DOI: 10.1038/s41593-025-02107-w
Stephan Krohn, Amy Romanello, Nina von Schwanenflug, Jerod M. Rasmussen, Claudia Buss, Sofie L. Valk, Christopher R. Madan, Carsten Finke
The neonatal period represents a critical phase of human brain development. During this time, the brain shows a dramatic increase in size, but how its morphology emerges in early life remains largely unknown. Here we show that human newborns undergo a rapid formation of brain shape, beyond the expected growth in brain size. Using fractal dimensionality (FD) analysis of structural neuroimaging data, we show that brain shape strongly reflects infant maturity beyond differences in brain size, significantly outperforms brain size in predicting infant age at scan (mean error approximately 4 days), detects signatures of premature birth that are not captured by brain size, is systematically more sensitive to genetic variability among infants and is superior in predicting which newborns are twin siblings, with up to 97% accuracy. Additionally, FD captures age and genetic information significantly better than earlier morphological measures, including cortical thickness, curvature, gyrification, sulcation, surface area and the T1-weighted/T2-weighted ratio. These findings identify the formation of brain shape as a fundamental maturational process in human brain development and show that, biologically, FD should be interpreted as a developmental marker of early-life brain maturity, which is rooted in geometry rather than size. Fractal analysis of structural MRI captures the formation of brain shape in human newborns and outperforms other morphological measures in predicting infant age and genetic similarity, including the identification of twins from their brain data.
{"title":"Fractal analysis of brain shape formation predicts age and genetic similarity in human newborns","authors":"Stephan Krohn, Amy Romanello, Nina von Schwanenflug, Jerod M. Rasmussen, Claudia Buss, Sofie L. Valk, Christopher R. Madan, Carsten Finke","doi":"10.1038/s41593-025-02107-w","DOIUrl":"10.1038/s41593-025-02107-w","url":null,"abstract":"The neonatal period represents a critical phase of human brain development. During this time, the brain shows a dramatic increase in size, but how its morphology emerges in early life remains largely unknown. Here we show that human newborns undergo a rapid formation of brain shape, beyond the expected growth in brain size. Using fractal dimensionality (FD) analysis of structural neuroimaging data, we show that brain shape strongly reflects infant maturity beyond differences in brain size, significantly outperforms brain size in predicting infant age at scan (mean error approximately 4 days), detects signatures of premature birth that are not captured by brain size, is systematically more sensitive to genetic variability among infants and is superior in predicting which newborns are twin siblings, with up to 97% accuracy. Additionally, FD captures age and genetic information significantly better than earlier morphological measures, including cortical thickness, curvature, gyrification, sulcation, surface area and the T1-weighted/T2-weighted ratio. These findings identify the formation of brain shape as a fundamental maturational process in human brain development and show that, biologically, FD should be interpreted as a developmental marker of early-life brain maturity, which is rooted in geometry rather than size. Fractal analysis of structural MRI captures the formation of brain shape in human newborns and outperforms other morphological measures in predicting infant age and genetic similarity, including the identification of twins from their brain data.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"29 1","pages":"171-185"},"PeriodicalIF":20.0,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41593-025-02107-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145857174","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 : 2025-12-29DOI: 10.1038/s41593-025-02159-y
Antoine Bergel, Julien M Schmidt, Baptiste Barrillot, Sébastien Arthaud, Laetitia Averty, Mark S Blumberg, Camille Carachet, Angeline Clair, Irina Filchenko, Chloé Froidevaux, Anthony Herrel, Bertrand Massot, Niels C Rattenborg, Markus H Schmidt, Mickael Tanter, Gianina Ungurean, Paul-Antoine Libourel
By recording brain activity in seven lizard species, humans, rats and pigeons, we demonstrate an infraslow brain rhythm during sleep in all species. This rhythm is tightly coupled with eye movements, muscle tone, heart and breathing rate in lizards, with skin brightness in chameleons and with pulsatile changes in cerebrovascular volume throughout sleep in bearded dragons and during non-rapid eye movement sleep in mice. These findings indicate that the infraslow rhythm is conserved across amniotes, questioning the evolution of sleep states.
{"title":"Sleep-dependent infraslow rhythms are evolutionarily conserved across reptiles and mammals.","authors":"Antoine Bergel, Julien M Schmidt, Baptiste Barrillot, Sébastien Arthaud, Laetitia Averty, Mark S Blumberg, Camille Carachet, Angeline Clair, Irina Filchenko, Chloé Froidevaux, Anthony Herrel, Bertrand Massot, Niels C Rattenborg, Markus H Schmidt, Mickael Tanter, Gianina Ungurean, Paul-Antoine Libourel","doi":"10.1038/s41593-025-02159-y","DOIUrl":"https://doi.org/10.1038/s41593-025-02159-y","url":null,"abstract":"<p><p>By recording brain activity in seven lizard species, humans, rats and pigeons, we demonstrate an infraslow brain rhythm during sleep in all species. This rhythm is tightly coupled with eye movements, muscle tone, heart and breathing rate in lizards, with skin brightness in chameleons and with pulsatile changes in cerebrovascular volume throughout sleep in bearded dragons and during non-rapid eye movement sleep in mice. These findings indicate that the infraslow rhythm is conserved across amniotes, questioning the evolution of sleep states.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":" ","pages":""},"PeriodicalIF":20.0,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145857314","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 : 2025-12-29DOI: 10.1038/s41593-025-02173-0
Priya Veeraraghavan, Anne K Engmann, John J Hatch, Yasuhiro Itoh, Duane Nguyen, Thomas Addison, Jeffrey D Macklis
Neurons of distinct subtypes compartmentalize subtype-specific function in part by differentially localizing and translating specific RNAs, but underlying mechanisms are not understood. Here we investigate messenger RNA localization and stability within subtype-specific growth cones (GCs), leading tips of growing axons, of long-range projection neurons (PNs) of the developing cerebral cortex. Comparison of GC-localized transcriptomes between two subtypes of PNs (interhemispheric-callosal and corticothalamic) across developmental stages identified both distinct and shared subcellular machinery involved in distinct phases of growth, target innervation and synaptogenesis, and enrichment of genes associated with neurodevelopmental and neuropsychiatric disorders. Further, we investigated sequence elements in dynamically GC-localized mRNAs, identifying GC-enriched motifs in 3' untranslated regions. For example, we identified that CPEB4, a translational regulator, regulates axonal branching and that RBMS1 functions dynamically in callosal circuit formation. This work offers generalizable insights for subcellular specialization in other polarized cells, toward elucidating neurodevelopmental and behavioral-cognitive disorders.
{"title":"Dynamic subtype- and context-specific subcellular RNA regulation in growth cones of developing neurons of the cerebral cortex.","authors":"Priya Veeraraghavan, Anne K Engmann, John J Hatch, Yasuhiro Itoh, Duane Nguyen, Thomas Addison, Jeffrey D Macklis","doi":"10.1038/s41593-025-02173-0","DOIUrl":"10.1038/s41593-025-02173-0","url":null,"abstract":"<p><p>Neurons of distinct subtypes compartmentalize subtype-specific function in part by differentially localizing and translating specific RNAs, but underlying mechanisms are not understood. Here we investigate messenger RNA localization and stability within subtype-specific growth cones (GCs), leading tips of growing axons, of long-range projection neurons (PNs) of the developing cerebral cortex. Comparison of GC-localized transcriptomes between two subtypes of PNs (interhemispheric-callosal and corticothalamic) across developmental stages identified both distinct and shared subcellular machinery involved in distinct phases of growth, target innervation and synaptogenesis, and enrichment of genes associated with neurodevelopmental and neuropsychiatric disorders. Further, we investigated sequence elements in dynamically GC-localized mRNAs, identifying GC-enriched motifs in 3' untranslated regions. For example, we identified that CPEB4, a translational regulator, regulates axonal branching and that RBMS1 functions dynamically in callosal circuit formation. This work offers generalizable insights for subcellular specialization in other polarized cells, toward elucidating neurodevelopmental and behavioral-cognitive disorders.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":" ","pages":""},"PeriodicalIF":20.0,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145857228","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}
Quantifying individual deviations in brain morphology from normative references is useful for understanding neurodiversity and facilitating personalized management of brain health. Here we report Chinese brain normative references using morphological imaging scans of 24,061 healthy volunteers from 105 sites, revealing later peak ages of lifespan neurodevelopmental milestones (1.2–8.9 years) than European/North American populations. We model individual brain deviation scores in 3,932 individuals with different neurological disorders from population references to evaluate three key aspects of brain health assessment using machine learning approaches: estimating disease propensity, predicting cognitive and physical outcomes and assessing treatment effects with distinct disability progression. The norm-deviation scores outperformed raw structural measures in these evaluations. Chinese-specific normative brain references may foster personalized diagnosis and prognosis in neurological diseases, enabling clinically applicable assessments of brain health. Liu et al. report Chinese normative lifespan brain charts showing later neurodevelopmental milestones than those detected in Western cohorts. Individual deviations from these norms are valuable in assessing clinical risk and outcomes.
Pub Date : 2025-12-29DOI: 10.1038/s41593-025-02164-1
David P. Finn, Brian E. McGuire, Simon Beggs, Katelynn E. Boerner, Karen D. Davis, Ruth Defrin, Yves De Koninck, Hemakumar Devan, Ryan Donovan, Eleonora Fetter, Herta Flor, Brona M. Fullen, Catherine R. Healy, Edmund Keogh, Rohini Kuner, Miriam Kunz, Rebecca M. Lane, Stefan Lautenbacher, Emeran A. Mayer, Jeffrey S. Mogil, Siobhain M. O’Mahony, Kieran O’Sullivan, Louise Riordan, Michael W. Salter, Francesco Scarlatti, George Shorten, Kathleen A. Sluka, Jennifer N. Stinson, Kevin E. Vowles, Suellen M. Walker, Ipek Yalcin, Michelle Roche
Sex and gender are important variables in research, but they are inconsistently explored. The international PAINDIFF Network makes 13 recommendations for studying sex and gender as variables in pain research, which are applicable across the spectrum of biopsychosocial research. Five universal recommendations apply to the majority of research studies: (1) include males and females as standard practice, (2) account for sex in randomization or counterbalancing and testing order, (3) power for sex differences when sex is a primary experimental variable, (4) include detailed reporting of experimental design, and (5) conduct sex-disaggregated analysis and reporting. Three additional recommendations specifically for preclinical studies and five additional recommendations for human and clinical studies are included. Recommendations for stakeholders, such as editors, reviewers, funding bodies and policymakers, have also been developed. Wide adoption and implementation of these recommendations will reduce variability, improve reproducibility and enhance the translatability of research findings within and beyond the field of pain. In this Perspective, the international PAINDIFF Network makes 13 recommendations for studying sex and gender as variables in preclinical, clinical and translational pain research that are applicable across the spectrum of biomedical and psychosocial research.
{"title":"Recommendations for the inclusion and study of sex and gender in research","authors":"David P. Finn, Brian E. McGuire, Simon Beggs, Katelynn E. Boerner, Karen D. Davis, Ruth Defrin, Yves De Koninck, Hemakumar Devan, Ryan Donovan, Eleonora Fetter, Herta Flor, Brona M. Fullen, Catherine R. Healy, Edmund Keogh, Rohini Kuner, Miriam Kunz, Rebecca M. Lane, Stefan Lautenbacher, Emeran A. Mayer, Jeffrey S. Mogil, Siobhain M. O’Mahony, Kieran O’Sullivan, Louise Riordan, Michael W. Salter, Francesco Scarlatti, George Shorten, Kathleen A. Sluka, Jennifer N. Stinson, Kevin E. Vowles, Suellen M. Walker, Ipek Yalcin, Michelle Roche","doi":"10.1038/s41593-025-02164-1","DOIUrl":"10.1038/s41593-025-02164-1","url":null,"abstract":"Sex and gender are important variables in research, but they are inconsistently explored. The international PAINDIFF Network makes 13 recommendations for studying sex and gender as variables in pain research, which are applicable across the spectrum of biopsychosocial research. Five universal recommendations apply to the majority of research studies: (1) include males and females as standard practice, (2) account for sex in randomization or counterbalancing and testing order, (3) power for sex differences when sex is a primary experimental variable, (4) include detailed reporting of experimental design, and (5) conduct sex-disaggregated analysis and reporting. Three additional recommendations specifically for preclinical studies and five additional recommendations for human and clinical studies are included. Recommendations for stakeholders, such as editors, reviewers, funding bodies and policymakers, have also been developed. Wide adoption and implementation of these recommendations will reduce variability, improve reproducibility and enhance the translatability of research findings within and beyond the field of pain. In this Perspective, the international PAINDIFF Network makes 13 recommendations for studying sex and gender as variables in preclinical, clinical and translational pain research that are applicable across the spectrum of biomedical and psychosocial research.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"29 2","pages":"256-266"},"PeriodicalIF":20.0,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145857336","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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