Pub Date : 2025-05-02DOI: 10.1038/s41583-025-00927-0
Jake Rogers
Dynorphin regulates motivated behaviour in mice via κ-opioid receptor signalling in a nucleus accumbens–ventral pallidum (VP) disinhibitory circuit that increases activity of VP cholinergic neurons projecting to the basolateral amygdala.
{"title":"Dynorphin acts via a disinhibitory circuit mechanism","authors":"Jake Rogers","doi":"10.1038/s41583-025-00927-0","DOIUrl":"10.1038/s41583-025-00927-0","url":null,"abstract":"Dynorphin regulates motivated behaviour in mice via κ-opioid receptor signalling in a nucleus accumbens–ventral pallidum (VP) disinhibitory circuit that increases activity of VP cholinergic neurons projecting to the basolateral amygdala.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"26 6","pages":"311-311"},"PeriodicalIF":26.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901417","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 : 2025-04-28DOI: 10.1038/s41583-025-00924-3
Jennifer N. Gelinas, Dion Khodagholy
Epilepsy is diagnosed when neural networks become capable of generating excessive or hypersynchronous activity patterns that result in observable seizures. In many cases, epilepsy is associated with cognitive comorbidities that persist between seizures and negatively impact quality of life. Dysregulation of the coordinated physiological network interactions that are required for cognitive function has been implicated in mediating these enduring symptoms, but the causal mechanisms are often elusive. Here, we provide an overview of neural network abnormalities with the potential to contribute to cognitive dysfunction in epilepsy. We examine these pathological interactions across spatial and temporal scales, additionally highlighting the dynamics that arise in response to the brain’s intrinsic capacity for plasticity. Understanding these processes will facilitate development of network-level interventions to address cognitive comorbidities that remain undertreated by currently available epilepsy therapeutics. Epilepsy is often associated with cognitive comorbidities that lack effective treatment options. In this Review, Gelinas and Khodagholy discuss how physiological neural networks involved in cognition are dysregulated in epilepsy and the therapeutic potential of network-level interventions.
{"title":"Interictal network dysfunction and cognitive impairment in epilepsy","authors":"Jennifer N. Gelinas, Dion Khodagholy","doi":"10.1038/s41583-025-00924-3","DOIUrl":"10.1038/s41583-025-00924-3","url":null,"abstract":"Epilepsy is diagnosed when neural networks become capable of generating excessive or hypersynchronous activity patterns that result in observable seizures. In many cases, epilepsy is associated with cognitive comorbidities that persist between seizures and negatively impact quality of life. Dysregulation of the coordinated physiological network interactions that are required for cognitive function has been implicated in mediating these enduring symptoms, but the causal mechanisms are often elusive. Here, we provide an overview of neural network abnormalities with the potential to contribute to cognitive dysfunction in epilepsy. We examine these pathological interactions across spatial and temporal scales, additionally highlighting the dynamics that arise in response to the brain’s intrinsic capacity for plasticity. Understanding these processes will facilitate development of network-level interventions to address cognitive comorbidities that remain undertreated by currently available epilepsy therapeutics. Epilepsy is often associated with cognitive comorbidities that lack effective treatment options. In this Review, Gelinas and Khodagholy discuss how physiological neural networks involved in cognition are dysregulated in epilepsy and the therapeutic potential of network-level interventions.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"26 7","pages":"399-414"},"PeriodicalIF":26.7,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884832","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 : 2025-04-17DOI: 10.1038/s41583-025-00923-4
Floris L. Wuyts, Choi Deblieck, Charlot Vandevoorde, Marco Durante
Solar system exploration is a grand endeavour of humankind. Space agencies have been planning crewed missions to the Moon and Mars for several decades. However, several environmental stress factors in space, such as microgravity and cosmic radiation, confer health risks for human explorers. This Review examines the effects of microgravity and exposure to cosmic radiation on the CNS. Microgravity presents challenges for the brain, necessitating the development of adaptive movement and orientation strategies to cope with alterations in sensory information. Exposure to microgravity also affects cognitive function to a certain extent. Recent MRI results show that microgravity affects brain structure and function. Post-flight recovery from these changes is gradual, with some lasting up to a year. Regarding cosmic radiation, animal experiments suggest that the brain could be much more sensitive to this stressor than may be expected from experiences on Earth. This may be due to the presence of energetic heavy ions in space that have an impact on cognitive function, even at low doses. However, all data about space radiation risk stem from rodent experiments, and extrapolation of these data to humans carries a high degree of uncertainty. Here, after presenting an overview of current knowledge in the above areas, we provide a concise description of possible counter-measures to protect the brain against microgravity and cosmic radiation during future space missions. Several space agencies are planning crewed, long-duration missions beyond low-Earth orbit, introducing various health risks and challenges to astronauts. In this Review, Durante and colleagues discuss the effects of two key stressors associated with space flight — microgravity and cosmic radiation — on the CNS.
{"title":"Brains in space: impact of microgravity and cosmic radiation on the CNS during space exploration","authors":"Floris L. Wuyts, Choi Deblieck, Charlot Vandevoorde, Marco Durante","doi":"10.1038/s41583-025-00923-4","DOIUrl":"10.1038/s41583-025-00923-4","url":null,"abstract":"Solar system exploration is a grand endeavour of humankind. Space agencies have been planning crewed missions to the Moon and Mars for several decades. However, several environmental stress factors in space, such as microgravity and cosmic radiation, confer health risks for human explorers. This Review examines the effects of microgravity and exposure to cosmic radiation on the CNS. Microgravity presents challenges for the brain, necessitating the development of adaptive movement and orientation strategies to cope with alterations in sensory information. Exposure to microgravity also affects cognitive function to a certain extent. Recent MRI results show that microgravity affects brain structure and function. Post-flight recovery from these changes is gradual, with some lasting up to a year. Regarding cosmic radiation, animal experiments suggest that the brain could be much more sensitive to this stressor than may be expected from experiences on Earth. This may be due to the presence of energetic heavy ions in space that have an impact on cognitive function, even at low doses. However, all data about space radiation risk stem from rodent experiments, and extrapolation of these data to humans carries a high degree of uncertainty. Here, after presenting an overview of current knowledge in the above areas, we provide a concise description of possible counter-measures to protect the brain against microgravity and cosmic radiation during future space missions. Several space agencies are planning crewed, long-duration missions beyond low-Earth orbit, introducing various health risks and challenges to astronauts. In this Review, Durante and colleagues discuss the effects of two key stressors associated with space flight — microgravity and cosmic radiation — on the CNS.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"26 6","pages":"354-371"},"PeriodicalIF":26.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841013","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 : 2025-04-09DOI: 10.1038/s41583-025-00919-0
Juan Alvaro Gallego
In this Journal Club, Juan Gallego discusses a 2014 article that provided a first causal hint that neural manifolds may not only be a convenient way to interpret neural population activity.
{"title":"Neural manifolds: more than the sum of their neurons","authors":"Juan Alvaro Gallego","doi":"10.1038/s41583-025-00919-0","DOIUrl":"10.1038/s41583-025-00919-0","url":null,"abstract":"In this Journal Club, Juan Gallego discusses a 2014 article that provided a first causal hint that neural manifolds may not only be a convenient way to interpret neural population activity.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"26 6","pages":"312-312"},"PeriodicalIF":26.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813635","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 : 2025-04-09DOI: 10.1038/s41583-025-00920-7
Adriano B. L. Tort, Diego A. Laplagne, Andreas Draguhn, Joaquin Gonzalez
Neuronal activities that synchronize with the breathing rhythm have been found in humans and a host of mammalian species, not only in brain areas closely related to respiratory control or olfactory coding but also in areas linked to emotional and higher cognitive functions. In parallel, evidence is mounting for modulations of perception and action by the breathing cycle. In this Review, we discuss the extent to which brain activity locks to breathing across areas, levels of organization and brain states, and the physiological origins of this global synchrony. We describe how waves of sensory activity evoked by nasal airflow spread through brain circuits, synchronizing neuronal populations to the breathing cycle and modulating faster oscillations, cell assembly formation and cross-area communication, thereby providing a mechanistic link from breathing to neural coding, emotion and cognition. We argue that, through evolution, the breathing rhythm has come to shape network functions across species. Synchrony between neuronal activity and the respiratory cycle has been observed in numerous brain regions and across many species. Tort et al. discuss the mechanisms by which brain activity is modulated by breathing and describe the functional impact of this synchrony on perception and cognition.
{"title":"Global coordination of brain activity by the breathing cycle","authors":"Adriano B. L. Tort, Diego A. Laplagne, Andreas Draguhn, Joaquin Gonzalez","doi":"10.1038/s41583-025-00920-7","DOIUrl":"10.1038/s41583-025-00920-7","url":null,"abstract":"Neuronal activities that synchronize with the breathing rhythm have been found in humans and a host of mammalian species, not only in brain areas closely related to respiratory control or olfactory coding but also in areas linked to emotional and higher cognitive functions. In parallel, evidence is mounting for modulations of perception and action by the breathing cycle. In this Review, we discuss the extent to which brain activity locks to breathing across areas, levels of organization and brain states, and the physiological origins of this global synchrony. We describe how waves of sensory activity evoked by nasal airflow spread through brain circuits, synchronizing neuronal populations to the breathing cycle and modulating faster oscillations, cell assembly formation and cross-area communication, thereby providing a mechanistic link from breathing to neural coding, emotion and cognition. We argue that, through evolution, the breathing rhythm has come to shape network functions across species. Synchrony between neuronal activity and the respiratory cycle has been observed in numerous brain regions and across many species. Tort et al. discuss the mechanisms by which brain activity is modulated by breathing and describe the functional impact of this synchrony on perception and cognition.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"26 6","pages":"333-353"},"PeriodicalIF":26.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813666","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 : 2025-04-02DOI: 10.1038/s41583-025-00918-1
Jake Rogers
A naturalistic threat–reward conflict reveals that dopamine dynamics in tail of the striatum in mice regulate not only avoidance of potential threats but also learning to overcome them.
{"title":"Dopamine signals threat-coping behaviour in threat–reward conflicts","authors":"Jake Rogers","doi":"10.1038/s41583-025-00918-1","DOIUrl":"10.1038/s41583-025-00918-1","url":null,"abstract":"A naturalistic threat–reward conflict reveals that dopamine dynamics in tail of the striatum in mice regulate not only avoidance of potential threats but also learning to overcome them.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"26 5","pages":"246-246"},"PeriodicalIF":26.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758356","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 : 2025-04-02DOI: 10.1038/s41583-025-00917-2
Sidharth Tyagi, Grant P. Higerd-Rusli, Elizabeth J. Akin, Stephen G. Waxman, Sulayman D. Dib-Hajj
The polarized and domain-specific distribution of membrane ion channels is essential for neuronal homeostasis, but delivery of these proteins to distal neuronal compartments (such as the axonal ends of peripheral sensory neurons) presents a logistical challenge. Recent developments have enabled the real-time imaging of single protein trafficking and the investigation of the life cycle of ion channels across neuronal compartments. These studies have revealed a highly regulated process involving post-translational modifications, vesicular sorting, motor protein-driven transport and targeted membrane insertion. Emerging evidence suggests that neuronal activity and disease states can dynamically modulate ion channel localization, directly influencing excitability. This Review synthesizes current knowledge on the spatiotemporal regulation of ion channel trafficking in both central and peripheral nervous system neurons. Understanding these processes not only advances our fundamental knowledge of neuronal excitability, but also reveals potential therapeutic targets for disorders involving aberrant ion channel distribution, such as chronic pain and neurodegenerative diseases. Neuronal function depends upon the domain-specific localization of membrane ion channels. Tyagi et al. describe our current understanding of the mechanisms that regulate ion channel delivery to specific neuronal compartments, with a focus on the distribution of voltage-gated sodium channels in peripheral sensory axons.
{"title":"Sculpting excitable membranes: voltage-gated ion channel delivery and distribution","authors":"Sidharth Tyagi, Grant P. Higerd-Rusli, Elizabeth J. Akin, Stephen G. Waxman, Sulayman D. Dib-Hajj","doi":"10.1038/s41583-025-00917-2","DOIUrl":"10.1038/s41583-025-00917-2","url":null,"abstract":"The polarized and domain-specific distribution of membrane ion channels is essential for neuronal homeostasis, but delivery of these proteins to distal neuronal compartments (such as the axonal ends of peripheral sensory neurons) presents a logistical challenge. Recent developments have enabled the real-time imaging of single protein trafficking and the investigation of the life cycle of ion channels across neuronal compartments. These studies have revealed a highly regulated process involving post-translational modifications, vesicular sorting, motor protein-driven transport and targeted membrane insertion. Emerging evidence suggests that neuronal activity and disease states can dynamically modulate ion channel localization, directly influencing excitability. This Review synthesizes current knowledge on the spatiotemporal regulation of ion channel trafficking in both central and peripheral nervous system neurons. Understanding these processes not only advances our fundamental knowledge of neuronal excitability, but also reveals potential therapeutic targets for disorders involving aberrant ion channel distribution, such as chronic pain and neurodegenerative diseases. Neuronal function depends upon the domain-specific localization of membrane ion channels. Tyagi et al. describe our current understanding of the mechanisms that regulate ion channel delivery to specific neuronal compartments, with a focus on the distribution of voltage-gated sodium channels in peripheral sensory axons.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"26 6","pages":"313-332"},"PeriodicalIF":26.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766505","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 : 2025-03-31DOI: 10.1038/s41583-025-00922-5
Sian Lewis
The hypothalamic preoptic area is involved in numerous homeostatic and social behaviours, and the neurons of this area are shown in this study to consist of numerous subtypes that show diverse maturational profiles that correlate with periods of substantial behavioural change such as weaning and puberty.
{"title":"Shaping preoptic-area neuronal diversity","authors":"Sian Lewis","doi":"10.1038/s41583-025-00922-5","DOIUrl":"10.1038/s41583-025-00922-5","url":null,"abstract":"The hypothalamic preoptic area is involved in numerous homeostatic and social behaviours, and the neurons of this area are shown in this study to consist of numerous subtypes that show diverse maturational profiles that correlate with periods of substantial behavioural change such as weaning and puberty.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"26 5","pages":"245-245"},"PeriodicalIF":26.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744852","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 : 2025-03-26DOI: 10.1038/s41583-025-00921-6
Isobel Leake
A study provides evidence to support a previously unknown function of the premotor cortex in the inhibitory control of speech.
一项研究提供了证据，支持运动前皮层在言语抑制控制中的一个以前未知的功能。
{"title":"Stopping speech on demand","authors":"Isobel Leake","doi":"10.1038/s41583-025-00921-6","DOIUrl":"10.1038/s41583-025-00921-6","url":null,"abstract":"A study provides evidence to support a previously unknown function of the premotor cortex in the inhibitory control of speech.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"26 5","pages":"245-245"},"PeriodicalIF":26.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713014","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 : 2025-03-26DOI: 10.1038/s41583-025-00911-8
Mara Mather
In addition to their more studied cognitive and motor effects, neurodegenerative diseases are also associated with impairments in autonomic function — the regulation of involuntary physiological processes. These autonomic impairments manifest in different ways and at different stages depending on the specific disease. The neural networks responsible for autonomic regulation in the brain and body have characteristics that render them particularly susceptible to the prion-like spread of protein aggregation involved in neurodegenerative diseases. Specifically, the axons of these neurons — in both peripheral and central networks — are long and poorly myelinated axons, which make them preferential targets for pathological protein aggregation. Moreover, cortical regions integrating information about the internal state of the body are highly connected with other brain regions, which increases the likelihood of intersection with pathological pathways and prion-like spread of abnormal proteins. This leads to an autonomic ‘signature’ of dysfunction, characteristic of each neurodegenerative disease, that is linked to the affected networks and regions undergoing pathological aggregation. Neurodegenerative disorders are commonly associated with autonomic dysfunction as well as the more well-known cognitive and motor effects. In this Review, Mather describes how properties of neurons in the brain and periphery regulating autonomic activity render them more vulnerable to prion-like spread of pathological protein and subsequent neurodegeneration.
{"title":"Autonomic dysfunction in neurodegenerative disease","authors":"Mara Mather","doi":"10.1038/s41583-025-00911-8","DOIUrl":"10.1038/s41583-025-00911-8","url":null,"abstract":"In addition to their more studied cognitive and motor effects, neurodegenerative diseases are also associated with impairments in autonomic function — the regulation of involuntary physiological processes. These autonomic impairments manifest in different ways and at different stages depending on the specific disease. The neural networks responsible for autonomic regulation in the brain and body have characteristics that render them particularly susceptible to the prion-like spread of protein aggregation involved in neurodegenerative diseases. Specifically, the axons of these neurons — in both peripheral and central networks — are long and poorly myelinated axons, which make them preferential targets for pathological protein aggregation. Moreover, cortical regions integrating information about the internal state of the body are highly connected with other brain regions, which increases the likelihood of intersection with pathological pathways and prion-like spread of abnormal proteins. This leads to an autonomic ‘signature’ of dysfunction, characteristic of each neurodegenerative disease, that is linked to the affected networks and regions undergoing pathological aggregation. Neurodegenerative disorders are commonly associated with autonomic dysfunction as well as the more well-known cognitive and motor effects. In this Review, Mather describes how properties of neurons in the brain and periphery regulating autonomic activity render them more vulnerable to prion-like spread of pathological protein and subsequent neurodegeneration.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"26 5","pages":"276-292"},"PeriodicalIF":26.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703198","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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