Pub Date : 2025-11-18DOI: 10.1038/s41583-025-01005-1
Matthew L. Kraushar
In this Journal Club, Matthew Kraushar discusses a study published in 1996 that found a role for local protein translation in hippocampal synaptic plasticity.
{"title":"The on-site, on-demand, neuronal gene machine","authors":"Matthew L. Kraushar","doi":"10.1038/s41583-025-01005-1","DOIUrl":"10.1038/s41583-025-01005-1","url":null,"abstract":"In this Journal Club, Matthew Kraushar discusses a study published in 1996 that found a role for local protein translation in hippocampal synaptic plasticity.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"27 1","pages":"6-6"},"PeriodicalIF":26.7,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145545360","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 : 2025-11-17DOI: 10.1038/s41583-025-00989-0
Edoardo Chidichimo, Andrea I. Luppi, Pedro A. M. Mediano, Victoria Leong, Guillaume Dumas, Andrés Canales-Johnson, Richard A. I. Bethlehem
Human sociality is grounded in the dynamic coordination of individuals as they interact with one another. Indeed, various levels of interpersonal coordination — neural, behavioural, physiological, affective, linguistic — are hallmarks of successful social communication and cooperation. However, describing these complex, interdependent dynamics has been limited by current methodological approaches, owing to a restrictive repertoire of tools and the absence of a unified, standardized methodological framework. Here, we identify information theory — the mathematical theory of communication — as a particularly well-suited conceptual framework to address this shortfall, given its appropriate sensitivity to complex dynamics, including potential nonlinearity and higher-order interactions, and its data-driven, model-agnostic foundations. With deep roots in computational, cognitive and systems neuroscience, the formal introduction of information-theoretic quantities and methods into the study of interpersonal coordination is perhaps overdue. In this Perspective, we advance the case for a unified information-theoretic framework for the field while paving the way for a new generation of empirically testable, theoretically grounded research questions. Methodological shortcomings have constrained studies describing the complex dynamics of interpersonal coordination, which is essential to human sociality. In this Perspective, Chidichimo et al. advance the case for the formal introduction of information-theoretic quantities and methods to overcome existing limitations in studies of naturalistic human interactions.
{"title":"Towards an informational account of interpersonal coordination","authors":"Edoardo Chidichimo, Andrea I. Luppi, Pedro A. M. Mediano, Victoria Leong, Guillaume Dumas, Andrés Canales-Johnson, Richard A. I. Bethlehem","doi":"10.1038/s41583-025-00989-0","DOIUrl":"10.1038/s41583-025-00989-0","url":null,"abstract":"Human sociality is grounded in the dynamic coordination of individuals as they interact with one another. Indeed, various levels of interpersonal coordination — neural, behavioural, physiological, affective, linguistic — are hallmarks of successful social communication and cooperation. However, describing these complex, interdependent dynamics has been limited by current methodological approaches, owing to a restrictive repertoire of tools and the absence of a unified, standardized methodological framework. Here, we identify information theory — the mathematical theory of communication — as a particularly well-suited conceptual framework to address this shortfall, given its appropriate sensitivity to complex dynamics, including potential nonlinearity and higher-order interactions, and its data-driven, model-agnostic foundations. With deep roots in computational, cognitive and systems neuroscience, the formal introduction of information-theoretic quantities and methods into the study of interpersonal coordination is perhaps overdue. In this Perspective, we advance the case for a unified information-theoretic framework for the field while paving the way for a new generation of empirically testable, theoretically grounded research questions. Methodological shortcomings have constrained studies describing the complex dynamics of interpersonal coordination, which is essential to human sociality. In this Perspective, Chidichimo et al. advance the case for the formal introduction of information-theoretic quantities and methods to overcome existing limitations in studies of naturalistic human interactions.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"27 2","pages":"121-137"},"PeriodicalIF":26.7,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145536185","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 : 2025-11-13DOI: 10.1038/s41583-025-00985-4
Nadia McMillan, Alexandra McMillan, Pien Kiliaan, Taha Yahya, Roshni Thakkar, Howard Weiner, Stelios Smirnakis, Dileep Yavagal, Saef Izzy
Stroke remains a leading cause of disability owing to the irreversible neuronal loss that it causes and the limited regenerative capacity of the CNS. Although reperfusion therapies such as thrombolysis and mechanical thrombectomy can restore blood flow after stroke, their stringent eligibility criteria leave many patients without treatment options. The immune response, involving complex interactions between brain-resident and peripheral immune cells, has a critical role in stroke recovery. Stem cell-based therapies, particularly those involving neural stem cells and mesenchymal stem cells, may be able to reshape the inflammatory microenvironment after stroke, mitigating secondary injury and promoting tissue repair. However, the precise mechanisms driving their effects remain incompletely understood, hindering clinical translation. In this Review, we highlight the bidirectional crosstalk between stem cells and immune cells (including microglia, T cells and peripheral immune cells) and discuss how these interactions influence neuroinflammation, neural plasticity and circuit remodelling in stroke recovery. We examine key determinants of stem cell therapy efficacy, emphasizing the role of stem cell–immune cell interactions, and discuss targeted strategies to enhance immune modulation and neuroprotection. In this Review, Saef Izzy and colleagues examine the therapeutic potential of stem cells in stroke, with a focus on neural and mesenchymal stem cells. They explore how these stem cells interact with brain immune cells to modulate the inflammatory microenvironment, restore blood–brain barrier integrity and promote tissue repair following a stroke.
{"title":"Stem cell-mediated recovery in stroke: partnering with the immune system","authors":"Nadia McMillan, Alexandra McMillan, Pien Kiliaan, Taha Yahya, Roshni Thakkar, Howard Weiner, Stelios Smirnakis, Dileep Yavagal, Saef Izzy","doi":"10.1038/s41583-025-00985-4","DOIUrl":"10.1038/s41583-025-00985-4","url":null,"abstract":"Stroke remains a leading cause of disability owing to the irreversible neuronal loss that it causes and the limited regenerative capacity of the CNS. Although reperfusion therapies such as thrombolysis and mechanical thrombectomy can restore blood flow after stroke, their stringent eligibility criteria leave many patients without treatment options. The immune response, involving complex interactions between brain-resident and peripheral immune cells, has a critical role in stroke recovery. Stem cell-based therapies, particularly those involving neural stem cells and mesenchymal stem cells, may be able to reshape the inflammatory microenvironment after stroke, mitigating secondary injury and promoting tissue repair. However, the precise mechanisms driving their effects remain incompletely understood, hindering clinical translation. In this Review, we highlight the bidirectional crosstalk between stem cells and immune cells (including microglia, T cells and peripheral immune cells) and discuss how these interactions influence neuroinflammation, neural plasticity and circuit remodelling in stroke recovery. We examine key determinants of stem cell therapy efficacy, emphasizing the role of stem cell–immune cell interactions, and discuss targeted strategies to enhance immune modulation and neuroprotection. In this Review, Saef Izzy and colleagues examine the therapeutic potential of stem cells in stroke, with a focus on neural and mesenchymal stem cells. They explore how these stem cells interact with brain immune cells to modulate the inflammatory microenvironment, restore blood–brain barrier integrity and promote tissue repair following a stroke.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"27 1","pages":"23-43"},"PeriodicalIF":26.7,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145509022","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 : 2025-11-12DOI: 10.1038/s41583-025-00986-3
Andrea Loreto, Lukas J. Neukomm
Programmed axon degeneration (PAxD) is an evolutionarily conserved mechanism in the nervous system that is activated by axonal injury (axotomy) to execute the self-destruction of a severed distal axon. It can also be triggered by non-axotomy insults, resulting in the loss of axons connected to their cell bodies. PAxD is therefore a promising target for therapeutic intervention and drugs that inhibit it are currently being tested in clinical trials. In this Review, we summarize the molecular mechanism of PAxD, focusing on its regulation by nicotinamide adenine dinucleotide (NAD+) metabolism and how it dictates Ca2+-mediated axonal demise. We examine its involvement in human disease and its potential as a therapeutic target by dissecting its role in various non-axotomy disease models. Finally, we address key challenges for its clinical translation, including the need for relevant biomarkers and safety considerations. Further advancements in understanding PAxD will pave the way for new therapeutic strategies targeting human axonopathies. Programmed axon degeneration (PAxD) is activated by axotomy to execute the self-destruction of a severed distal axon. It may also be activated by some non-axotomy insults, suggesting it has a role in some neurodegenerative diseases. Here, Loreto and Neukomm review the molecular mechanisms of PAxD, its involvement in disease and its potential as a therapeutic target.
{"title":"Programmed axon degeneration: mechanism, inhibition and therapeutic potential","authors":"Andrea Loreto, Lukas J. Neukomm","doi":"10.1038/s41583-025-00986-3","DOIUrl":"10.1038/s41583-025-00986-3","url":null,"abstract":"Programmed axon degeneration (PAxD) is an evolutionarily conserved mechanism in the nervous system that is activated by axonal injury (axotomy) to execute the self-destruction of a severed distal axon. It can also be triggered by non-axotomy insults, resulting in the loss of axons connected to their cell bodies. PAxD is therefore a promising target for therapeutic intervention and drugs that inhibit it are currently being tested in clinical trials. In this Review, we summarize the molecular mechanism of PAxD, focusing on its regulation by nicotinamide adenine dinucleotide (NAD+) metabolism and how it dictates Ca2+-mediated axonal demise. We examine its involvement in human disease and its potential as a therapeutic target by dissecting its role in various non-axotomy disease models. Finally, we address key challenges for its clinical translation, including the need for relevant biomarkers and safety considerations. Further advancements in understanding PAxD will pave the way for new therapeutic strategies targeting human axonopathies. Programmed axon degeneration (PAxD) is activated by axotomy to execute the self-destruction of a severed distal axon. It may also be activated by some non-axotomy insults, suggesting it has a role in some neurodegenerative diseases. Here, Loreto and Neukomm review the molecular mechanisms of PAxD, its involvement in disease and its potential as a therapeutic target.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"27 1","pages":"44-60"},"PeriodicalIF":26.7,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145492640","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 : 2025-11-12DOI: 10.1038/s41583-025-00987-2
György Buzsáki
Time and space are crucial concepts in neuroscience, because our personal memories are tied to specific events that occur ‘in’ a particular space and on a ‘timeline’. Thus, we seek to understand how the brain constructs time and space and how these are related to episodic memory. Place cells and time cells have been identified in the brain and have been proposed to ‘represent’ space and time via single-neuron or population coding, thus acting as hypothetical coordinates within a Newtonian framework of space and time. However, there is a fundamental tension between the linear and unidirectional flow of physical time and the variable nature of experienced time. Moreover, modern physics no longer views space as a fixed container and time as something in which events occur. Here, I articulate an alternative view: that time (physical and experienced) is an abstracted relational measure of change. Physical time is measured using arbitrary units and artificial clocks, whereas experienced time is linked to a hierarchy of brain–body rhythms that provide a range of reference scales that reflect the full span of experienced time. Changes in body and brain circuits, tied to these rhythms, may be the source of our subjective feeling of time. Understanding how the brain represents experienced time and how representations of space and time are integrated to form episodic memories has been a goal of much neuroscientific research. In this Perspective, Buzsáki discusses classical and contemporary ideas about time perception and proposes that a hierarchy of brain–body rhythms contributes to our subjective experience of time.
{"title":"Time, space, memory and brain–body rhythms","authors":"György Buzsáki","doi":"10.1038/s41583-025-00987-2","DOIUrl":"10.1038/s41583-025-00987-2","url":null,"abstract":"Time and space are crucial concepts in neuroscience, because our personal memories are tied to specific events that occur ‘in’ a particular space and on a ‘timeline’. Thus, we seek to understand how the brain constructs time and space and how these are related to episodic memory. Place cells and time cells have been identified in the brain and have been proposed to ‘represent’ space and time via single-neuron or population coding, thus acting as hypothetical coordinates within a Newtonian framework of space and time. However, there is a fundamental tension between the linear and unidirectional flow of physical time and the variable nature of experienced time. Moreover, modern physics no longer views space as a fixed container and time as something in which events occur. Here, I articulate an alternative view: that time (physical and experienced) is an abstracted relational measure of change. Physical time is measured using arbitrary units and artificial clocks, whereas experienced time is linked to a hierarchy of brain–body rhythms that provide a range of reference scales that reflect the full span of experienced time. Changes in body and brain circuits, tied to these rhythms, may be the source of our subjective feeling of time. Understanding how the brain represents experienced time and how representations of space and time are integrated to form episodic memories has been a goal of much neuroscientific research. In this Perspective, Buzsáki discusses classical and contemporary ideas about time perception and proposes that a hierarchy of brain–body rhythms contributes to our subjective experience of time.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"27 1","pages":"61-78"},"PeriodicalIF":26.7,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145498282","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 : 2025-11-11DOI: 10.1038/s41583-025-00999-y
Sian Lewis
People with chronic pain often also have anxiety and/or depression; here, the authors show that psilocybin, the psychoactive component of ‘magic mushrooms’, produces rapid and sustained improvement in both pain and anxiodepressive-like behaviours in mice.
{"title":"‘Magic’ mechanisms underlie psilocybin’s effects in chronic pain","authors":"Sian Lewis","doi":"10.1038/s41583-025-00999-y","DOIUrl":"10.1038/s41583-025-00999-y","url":null,"abstract":"People with chronic pain often also have anxiety and/or depression; here, the authors show that psilocybin, the psychoactive component of ‘magic mushrooms’, produces rapid and sustained improvement in both pain and anxiodepressive-like behaviours in mice.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"27 1","pages":"3-3"},"PeriodicalIF":26.7,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491576","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 : 2025-11-07DOI: 10.1038/s41583-025-00995-2
Sian Lewis
Both full-collapse fusion and the more transient ‘kiss-and-run’ fusion are shown to occur at hippocampal synapses, with the kiss-and-run form involving vesicle shrinkage in between ‘kissing’ and ‘running’.
{"title":"Dock, prime, deliver while shrinking — and repeat","authors":"Sian Lewis","doi":"10.1038/s41583-025-00995-2","DOIUrl":"10.1038/s41583-025-00995-2","url":null,"abstract":"Both full-collapse fusion and the more transient ‘kiss-and-run’ fusion are shown to occur at hippocampal synapses, with the kiss-and-run form involving vesicle shrinkage in between ‘kissing’ and ‘running’.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"27 1","pages":"4-4"},"PeriodicalIF":26.7,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145455359","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 : 2025-10-31DOI: 10.1038/s41583-025-00991-6
Frank F. Lanfranchi
In this Tools of the Trade article, Frank F. Lanfranchi describes Neuropixels 1.0 NHP, which allows the tracking of co-ordinated activity of hundreds of neurons across different brain areas in non-human primates, revealing the complexity of neural dynamics during complex tasks.
在这篇贸易工具的文章中，Frank F. Lanfranchi描述了Neuropixels 1.0 NHP，它可以跟踪非人类灵长类动物不同大脑区域数百个神经元的协调活动，揭示复杂任务中神经动力学的复杂性。
{"title":"Recording single neurons at scale in the primate brain","authors":"Frank F. Lanfranchi","doi":"10.1038/s41583-025-00991-6","DOIUrl":"10.1038/s41583-025-00991-6","url":null,"abstract":"In this Tools of the Trade article, Frank F. Lanfranchi describes Neuropixels 1.0 NHP, which allows the tracking of co-ordinated activity of hundreds of neurons across different brain areas in non-human primates, revealing the complexity of neural dynamics during complex tasks.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"26 12","pages":"734-734"},"PeriodicalIF":26.7,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145411627","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":"Affective tactile comfort: is a specialized sensory system involved?","authors":"Takayuki Yamashita","doi":"10.1038/s41583-025-00993-4","DOIUrl":"10.1038/s41583-025-00993-4","url":null,"abstract":"In this Journal Club, Takayuki Yamashita discusses a 2002 study about the role of unmyelinated C-tactile afferents in touch.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"27 1","pages":"5-5"},"PeriodicalIF":26.7,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145411629","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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