Pub Date : 2025-11-20DOI: 10.1152/physrev.00007.2025
Elena Krugliakova,Friederike Breuer,Nico Adelhöfer,Alejandra Alonso,Luciana Besedovsky,Keith Murphy,Emma Peters,Karolina Raczek,Björn Rasch,Leila Salvesen,Sophia Snipes,Sarah Schoch,Thomas Schreiner,Rick Wassing,Til Ole Bergmann,Martin Dresler
Sleep is essentially contributing to human health and wellbeing through multiple biological functions, including restoration and biosynthesis, brain clearance, energy metabolism, immunological and endocrine processing, synaptic plasticity, memory consolidation, and regulation of cognitive and emotional processes. Sleep disturbances are highly prevalent and are both a symptom and a contributing risk factor for psychiatric, neurological, and somatic disorders. Given the limitations of pharmacological interventions, non-invasive neuromodulation techniques ranging from non-invasive transcranial (TMS, tDCS, tACS, tRNS, tTIS, and TUS) to peripheral sensory (auditory, olfactory, visual, tactile, vestibular) and electrical nerve (galvanic vestibular, transcutaneous vagus nerve, and median nerve) stimulation have gained increasing attention as potential tools to modulate sleep physiology. These techniques offer promising avenues for both therapeutic applications and fundamental research into sleep-dependent neuroplasticity, interregional communication, and oscillatory activity. However, sleep is not a uniform state but a highly complex and dynamic phenomenon, with intricate macrostructural (e.g., NREM-REM sleep balance, sleep efficiency) and microstructural characteristics (e.g., hierarchically nested slow waves and spindles) that contribute to a variety of functions. This complexity necessitates precise targeting strategies, often employing real-time brain-state-de pendent stimulation, to modulate specific sleep-related processes effectively. In this review, we summarise the functions of sleep and the available non-invasive tools for its modulation, addressing key methodological challenges and providing recommendations for best practices in sleep neuromodulation.
{"title":"Hacking the functions of sleep: Non-invasive approaches to stimulate sleep neurophysiology.","authors":"Elena Krugliakova,Friederike Breuer,Nico Adelhöfer,Alejandra Alonso,Luciana Besedovsky,Keith Murphy,Emma Peters,Karolina Raczek,Björn Rasch,Leila Salvesen,Sophia Snipes,Sarah Schoch,Thomas Schreiner,Rick Wassing,Til Ole Bergmann,Martin Dresler","doi":"10.1152/physrev.00007.2025","DOIUrl":"https://doi.org/10.1152/physrev.00007.2025","url":null,"abstract":"Sleep is essentially contributing to human health and wellbeing through multiple biological functions, including restoration and biosynthesis, brain clearance, energy metabolism, immunological and endocrine processing, synaptic plasticity, memory consolidation, and regulation of cognitive and emotional processes. Sleep disturbances are highly prevalent and are both a symptom and a contributing risk factor for psychiatric, neurological, and somatic disorders. Given the limitations of pharmacological interventions, non-invasive neuromodulation techniques ranging from non-invasive transcranial (TMS, tDCS, tACS, tRNS, tTIS, and TUS) to peripheral sensory (auditory, olfactory, visual, tactile, vestibular) and electrical nerve (galvanic vestibular, transcutaneous vagus nerve, and median nerve) stimulation have gained increasing attention as potential tools to modulate sleep physiology. These techniques offer promising avenues for both therapeutic applications and fundamental research into sleep-dependent neuroplasticity, interregional communication, and oscillatory activity. However, sleep is not a uniform state but a highly complex and dynamic phenomenon, with intricate macrostructural (e.g., NREM-REM sleep balance, sleep efficiency) and microstructural characteristics (e.g., hierarchically nested slow waves and spindles) that contribute to a variety of functions. This complexity necessitates precise targeting strategies, often employing real-time brain-state-de pendent stimulation, to modulate specific sleep-related processes effectively. In this review, we summarise the functions of sleep and the available non-invasive tools for its modulation, addressing key methodological challenges and providing recommendations for best practices in sleep neuromodulation.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"8 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559009","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}
Episodic memory is a declarative long-term memory of a specific past experience. As such, it is multifaceted, encompassing both the objective and subjective components of that experience. These components can be flexibly represented at different levels of granularity, from precise, context-specific details to generalized, gist-like representations. In this review, we suggest that 1) multiple representations of an episodic memory at different levels of granularity are simultaneously encoded into a memory trace and 2) the relative weighting of these representations determines the extent to which a memory is reconstructed or reproduced at retrieval. We propose that this representational flexibility drives adaptive behavior by prioritizing reconstruction or reproduction depending on the age of the memory, its relationship to prior knowledge, current attentional goals, or task demands, and individual differences. Drawing on research in humans and non-human animals, we show a close correspondence between psychological and neural representations of a memory across encoding, consolidation, and retrieval. Specifically, we discuss how hippocampal activity in humans and engram formation and activation in rodents support the reproduction of detailed memory representations, while schema formation across species, mediated by the medial prefrontal cortex, facilitates reconstruction and generalization to guide behavior. Finally, we consider how species- and individual-level differences shape episodic memory representations. By integrating findings across species, we illustrate how the correspondence between neural and psychological representations enables multiple memory representations to balance stability and flexibility, ultimately driving adaptive behavior.
{"title":"Adaptive episodic memory: How multiple memory representations drive behaviour in humans and non-humans.","authors":"Hannah Tarder-Stoll,Melanie J Sekeres,Brian Levine,Morris Moscovitch","doi":"10.1152/physrev.00005.2025","DOIUrl":"https://doi.org/10.1152/physrev.00005.2025","url":null,"abstract":"Episodic memory is a declarative long-term memory of a specific past experience. As such, it is multifaceted, encompassing both the objective and subjective components of that experience. These components can be flexibly represented at different levels of granularity, from precise, context-specific details to generalized, gist-like representations. In this review, we suggest that 1) multiple representations of an episodic memory at different levels of granularity are simultaneously encoded into a memory trace and 2) the relative weighting of these representations determines the extent to which a memory is reconstructed or reproduced at retrieval. We propose that this representational flexibility drives adaptive behavior by prioritizing reconstruction or reproduction depending on the age of the memory, its relationship to prior knowledge, current attentional goals, or task demands, and individual differences. Drawing on research in humans and non-human animals, we show a close correspondence between psychological and neural representations of a memory across encoding, consolidation, and retrieval. Specifically, we discuss how hippocampal activity in humans and engram formation and activation in rodents support the reproduction of detailed memory representations, while schema formation across species, mediated by the medial prefrontal cortex, facilitates reconstruction and generalization to guide behavior. Finally, we consider how species- and individual-level differences shape episodic memory representations. By integrating findings across species, we illustrate how the correspondence between neural and psychological representations enables multiple memory representations to balance stability and flexibility, ultimately driving adaptive behavior.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"18 4 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440772","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 : 2025-10-01DOI: 10.1152/physrev.00011.2024_cor
{"title":"Corrigendum for Lutsenko et al., volume 105, 2025, p. 441-491.","authors":"","doi":"10.1152/physrev.00011.2024_cor","DOIUrl":"https://doi.org/10.1152/physrev.00011.2024_cor","url":null,"abstract":"","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"1 1","pages":"2231"},"PeriodicalIF":33.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533289","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 : 2025-10-01Epub Date: 2025-06-11DOI: 10.1152/physrev.00039.2024
Irving L M H Aye, Stephen Tong, D Stephen Charnock-Jones, Gordon C S Smith
The placenta performs many key tasks that are essential for the healthy growth and development of the human fetus. Placental dysfunction has multiple manifestations, but they share the common property of lacking a mechanistic understanding of etiology. The clinical consequences of placental dysfunction are a major determinant of the global burden of disease. Currently, the primary clinical method for assessing placental function is ultrasonic Doppler flow velocimetry of the umbilical and uterine arteries. More recently, some biomarkers have emerged that can predict or diagnose placentally related complications of pregnancy. However, methods for identifying and characterizing placental dysfunction have developed relatively little over the last 20 years and perform poorly, and there remains an absence of disease-modifying therapies targeted at the placenta. Understanding disease mechanisms is made more difficult due to the profound differences in pregnancy and placentation comparing humans and the most commonly used laboratory animals, limiting the utility of animal models. The use of omics methods in human samples may yield progress: omics analyses of maternal blood show promise in identifying better predictors of disease, and single-cell analyses, including spatial omics of healthy and abnormal placentas, could identify therapeutic targets. Limitations in cellular models of the placenta have been significantly overcome in the last 5 to 10 years by the development of human cell models, including human trophoblast stem cells and organoids, and the use of these model systems may allow hypothesis testing experiments in a more clinically relevant context than animal models or immortalized cell lines.
{"title":"The human placenta and its role in reproductive outcomes revisited.","authors":"Irving L M H Aye, Stephen Tong, D Stephen Charnock-Jones, Gordon C S Smith","doi":"10.1152/physrev.00039.2024","DOIUrl":"10.1152/physrev.00039.2024","url":null,"abstract":"<p><p>The placenta performs many key tasks that are essential for the healthy growth and development of the human fetus. Placental dysfunction has multiple manifestations, but they share the common property of lacking a mechanistic understanding of etiology. The clinical consequences of placental dysfunction are a major determinant of the global burden of disease. Currently, the primary clinical method for assessing placental function is ultrasonic Doppler flow velocimetry of the umbilical and uterine arteries. More recently, some biomarkers have emerged that can predict or diagnose placentally related complications of pregnancy. However, methods for identifying and characterizing placental dysfunction have developed relatively little over the last 20 years and perform poorly, and there remains an absence of disease-modifying therapies targeted at the placenta. Understanding disease mechanisms is made more difficult due to the profound differences in pregnancy and placentation comparing humans and the most commonly used laboratory animals, limiting the utility of animal models. The use of omics methods in human samples may yield progress: omics analyses of maternal blood show promise in identifying better predictors of disease, and single-cell analyses, including spatial omics of healthy and abnormal placentas, could identify therapeutic targets. Limitations in cellular models of the placenta have been significantly overcome in the last 5 to 10 years by the development of human cell models, including human trophoblast stem cells and organoids, and the use of these model systems may allow hypothesis testing experiments in a more clinically relevant context than animal models or immortalized cell lines.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"2305-2376"},"PeriodicalIF":28.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7617900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267132","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 : 2025-09-30DOI: 10.1152/physrev.00001.2024
Gergely Gyimesi,Susan Tweedie,Elspeth Bruford,Matthias A Hediger
Membrane transporters are essential for human health, mediating the movement of nutrients, electrolytes, metabolites and other molecules across cellular and organellar membranes. Genes encoding these proteins account for approximately 5.2% of the human protein coding genome. Nearly half of these belong to the solute carriers (SLC) supergroup, the largest class of membrane transport proteins, collectively termed the "SLC-ome." The current SLC-ome comprises 464 SLCs organized into 76 SLC families, of which 24% (111 SLCs) remain orphan transporters with unknown or incompletely characterized function. An additional 52 SLC-like proteins bring the total to 516 membrane transport proteins. SLCs function as molecular gatekeepers, and their dysfunction contributes to a wide spectrum of human diseases, including cancer, diabetes, and immunological, cardiovascular and neurodegenerative disorders. Pathological consequences of SLC defects include hypertension, hyperglycemia, hypercholesterolemia, nutritional deficiencies, metal ion imbalance, oxidative stress, and dysfunction of mitochondria, lysosomes, endoplasmic reticulum and Golgi apparatus. In addition, genetic defects in SLCs are the cause of many rare diseases. Several SLCs require additional subunits to form functional heteromeric complexes, while others exhibit additional or alternative roles, such as acting as transceptors. In this review, we provide updated physiological, structural, mechanistic, and pharmacological insights for each of the 516 human SLC and SLC-like proteins. We also summarize their classification, structural architecture, transport mechanisms and pharmaceutical relevance, and present the most recent SLC gene nomenclature assignments approved by the HUGO Gene Nomenclature Committee (HGNC).
{"title":"The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.","authors":"Gergely Gyimesi,Susan Tweedie,Elspeth Bruford,Matthias A Hediger","doi":"10.1152/physrev.00001.2024","DOIUrl":"https://doi.org/10.1152/physrev.00001.2024","url":null,"abstract":"Membrane transporters are essential for human health, mediating the movement of nutrients, electrolytes, metabolites and other molecules across cellular and organellar membranes. Genes encoding these proteins account for approximately 5.2% of the human protein coding genome. Nearly half of these belong to the solute carriers (SLC) supergroup, the largest class of membrane transport proteins, collectively termed the \"SLC-ome.\" The current SLC-ome comprises 464 SLCs organized into 76 SLC families, of which 24% (111 SLCs) remain orphan transporters with unknown or incompletely characterized function. An additional 52 SLC-like proteins bring the total to 516 membrane transport proteins. SLCs function as molecular gatekeepers, and their dysfunction contributes to a wide spectrum of human diseases, including cancer, diabetes, and immunological, cardiovascular and neurodegenerative disorders. Pathological consequences of SLC defects include hypertension, hyperglycemia, hypercholesterolemia, nutritional deficiencies, metal ion imbalance, oxidative stress, and dysfunction of mitochondria, lysosomes, endoplasmic reticulum and Golgi apparatus. In addition, genetic defects in SLCs are the cause of many rare diseases. Several SLCs require additional subunits to form functional heteromeric complexes, while others exhibit additional or alternative roles, such as acting as transceptors. In this review, we provide updated physiological, structural, mechanistic, and pharmacological insights for each of the 516 human SLC and SLC-like proteins. We also summarize their classification, structural architecture, transport mechanisms and pharmaceutical relevance, and present the most recent SLC gene nomenclature assignments approved by the HUGO Gene Nomenclature Committee (HGNC).","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"24 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194673","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 : 2025-09-29DOI: 10.1152/physrev.00055.2024
Nandu Goswami, Andrew Philip Blaber, Giovanna Valenti, Helmut Hinghofer-Szalkay, Joyce Evans, Damian Miles Bailey, Joan Vernikos, Alexander Choukér, David Andrew Green, Olivier White, Jack J. W. A. van Loon, Victor A. Convertino
Physiological Reviews, Ahead of Print.
《生理评论》，出版前。
{"title":"Gravity, Microgravity and Artificial Gravity: Physiological Effects, Implementation and Applications","authors":"Nandu Goswami, Andrew Philip Blaber, Giovanna Valenti, Helmut Hinghofer-Szalkay, Joyce Evans, Damian Miles Bailey, Joan Vernikos, Alexander Choukér, David Andrew Green, Olivier White, Jack J. W. A. van Loon, Victor A. Convertino","doi":"10.1152/physrev.00055.2024","DOIUrl":"https://doi.org/10.1152/physrev.00055.2024","url":null,"abstract":"Physiological Reviews, Ahead of Print. <br/>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"99 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188720","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 : 2025-09-23DOI: 10.1152/physrev.00041.2024
Wouter C. Meijers, Joseph Pierre Aboumsallem, Alexander R. Lyon, Javid Moslehi, Rudolf A. de Boer
Physiological Reviews, Ahead of Print.
《生理评论》，出版前。
{"title":"Forward and reverse cardio-oncology","authors":"Wouter C. Meijers, Joseph Pierre Aboumsallem, Alexander R. Lyon, Javid Moslehi, Rudolf A. de Boer","doi":"10.1152/physrev.00041.2024","DOIUrl":"https://doi.org/10.1152/physrev.00041.2024","url":null,"abstract":"Physiological Reviews, Ahead of Print. <br/>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"40 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145116159","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 : 2025-09-12DOI: 10.1152/physrev.00056.2024
De Hao, Yimeng Liu, Li Li, Barry R. Stripp, Huaiyong Chen
Physiological Reviews, Ahead of Print.
《生理评论》，出版前。
{"title":"Immunological and regenerative properties of lung stem cells","authors":"De Hao, Yimeng Liu, Li Li, Barry R. Stripp, Huaiyong Chen","doi":"10.1152/physrev.00056.2024","DOIUrl":"https://doi.org/10.1152/physrev.00056.2024","url":null,"abstract":"Physiological Reviews, Ahead of Print. <br/>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"11 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043420","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 : 2025-08-29DOI: 10.1152/physrev.00042.2024
Namasivayam Ambalavanan, Gail Deutsch, Gloria Pryhuber, Colm P. Travers, Kent A. Willis
Physiological Reviews, Ahead of Print.
《生理评论》，出版前。
{"title":"The Evolving Pathophysiology of Bronchopulmonary Dysplasia","authors":"Namasivayam Ambalavanan, Gail Deutsch, Gloria Pryhuber, Colm P. Travers, Kent A. Willis","doi":"10.1152/physrev.00042.2024","DOIUrl":"https://doi.org/10.1152/physrev.00042.2024","url":null,"abstract":"Physiological Reviews, Ahead of Print. <br/>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"57 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919242","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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