PLoS BiologyPub Date : 2025-10-09eCollection Date: 2025-10-01DOI: 10.1371/journal.pbio.3003401
Sonja Wild, Gustavo Alarcón-Nieto, Lucy M Aplin
{"title":"Siblings and nonparental adults provide alternative pathways to cultural inheritance in juvenile great tits.","authors":"Sonja Wild, Gustavo Alarcón-Nieto, Lucy M Aplin","doi":"10.1371/journal.pbio.3003401","DOIUrl":"10.1371/journal.pbio.3003401","url":null,"abstract":"<p><p>In many animal species, the juvenile period is under strong selection, leading to a concentration of social learning during this stage as an efficient strategy for young individuals to acquire skills essential for survival. However, as social learning is not always adaptive, juveniles need to be strategic in when, who, and what to copy. In species with extended parental care, parents are often preferred sources of information, leading to stable intergenerational transmission of knowledge. However, little is known about transmission pathways in species with limited periods of parental care, and their implication for cultural inheritance. Here, we investigate social learning strategies during development in a model species with a dependence period of a few weeks, the great tit (Parus major). Using fully automated two-option foraging puzzles, we diffused knowledge about the puzzle through breeding populations and then constrained parental individuals' choices such that parents either (1) both had knowledge of the same option, (2) had conflicting knowledge of the two options, or (3) had no knowledge of how to solve the puzzle. We then tracked solving behavior of 229 newly fledged juveniles over 10 weeks. Parental solving frequency during dependence strongly predicted knowledge acquisition by offspring, suggesting intergenerational cultural inheritance. However, detailed investigation of learning pathways revealed siblings as the most important role models for social learning, followed by nonparental adults and parents. Furthermore, offsprings' option choices were not predicted by parental choices, but instead influenced by the broader social environment, with evidence for a conformist learning bias. Overall, by using large-scale experimental manipulation of parental behavior, our study offers new insights into social learning pathways and mechanisms of cultural inheritance in r-selected species with limited parental care and multiple offspring. Our findings provide a stark contrast to most previously studied systems exhibiting multigenerational cultures, where cultural transmission overwhelmingly occurs from parents to offspring, and give insights into the more variable transmission routes that might occur across socially learning species.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 10","pages":"e3003401"},"PeriodicalIF":7.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12510479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145259925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2025-10-09eCollection Date: 2025-10-01DOI: 10.1371/journal.pbio.3003431
Romain Fayat, Marie Sarraudy, Clément Léna, Daniela Popa, Pierre Latouche, Guillaume P Dugué
{"title":"DISSeCT: An unsupervised framework for high-resolution mapping of rodent behavior using inertial sensors.","authors":"Romain Fayat, Marie Sarraudy, Clément Léna, Daniela Popa, Pierre Latouche, Guillaume P Dugué","doi":"10.1371/journal.pbio.3003431","DOIUrl":"10.1371/journal.pbio.3003431","url":null,"abstract":"<p><p>Decomposing behavior into elementary components remains a central challenge in computational neuroethology. The current standard in laboratory animals involves multi-view video tracking, which, while providing unparalleled access to full-body kinematics, imposes environmental constraints, is data-intensive, and has limited scalability. We present an alternative approach using inertial sensors, which capture high-resolution, environment-independent, compact 3D kinematic data, and are commonly integrated into rodent neurophysiological devices. Our analysis pipeline leverages unsupervised, computationally efficient change-point detection to break down inertial time series into variable-length, statistically homogeneous segments. These segments are then grouped into candidate behavioral motifs through high-dimensional, model-based probabilistic clustering. We demonstrate that this approach achieves detailed rodent behavioral mapping using head inertial data. Identified motifs, corroborated by video recordings, include orienting movements, grooming components, locomotion, and olfactory exploration. Higher-order behavioral structures can be accessed by applying a categorical hidden Markov model to the motif sequence. Additionally, our pipeline detects both overt and subtle motor changes in a mouse model of Parkinson's disease and levodopa-induced dyskinesia, highlighting its utility for behavioral phenotyping. This methodology offers the possibility of conducting high-resolution, observer-unbiased behavioral analysis at minimal computational cost from easily scalable and environmentally unconstrained recordings.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 10","pages":"e3003431"},"PeriodicalIF":7.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145259830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2025-10-09eCollection Date: 2025-10-01DOI: 10.1371/journal.pbio.3003192
Ruiying Ma, Muwon Kang, Gyu Hyun Kim, Hyojin Kang, Sunho Lee, Yeji Yang, Hea Ji Lee, Seungji Choi, Seungsoo Kim, Seoyeong Kim, Yukyung Jun, Hyewon Kim, Yinhua Zhang, U Suk Kim, Hyae Rim Kang, Yoonhee Kim, Yulim Lee, Woosuk Chung, Eun Jung Lee, Serk In Park, Eunha Kim, Minji Jeon, Geum-Sook Hwang, Jungmin Choi, Youngae Jung, Jin Young Kim, Eunjoon Kim, Kea Joo Lee, Kihoon Han
{"title":"Seizure evolution in a mouse model of West syndrome involves complex and time-dependent synapse remodeling, gliosis and alterations in lipid metabolism.","authors":"Ruiying Ma, Muwon Kang, Gyu Hyun Kim, Hyojin Kang, Sunho Lee, Yeji Yang, Hea Ji Lee, Seungji Choi, Seungsoo Kim, Seoyeong Kim, Yukyung Jun, Hyewon Kim, Yinhua Zhang, U Suk Kim, Hyae Rim Kang, Yoonhee Kim, Yulim Lee, Woosuk Chung, Eun Jung Lee, Serk In Park, Eunha Kim, Minji Jeon, Geum-Sook Hwang, Jungmin Choi, Youngae Jung, Jin Young Kim, Eunjoon Kim, Kea Joo Lee, Kihoon Han","doi":"10.1371/journal.pbio.3003192","DOIUrl":"10.1371/journal.pbio.3003192","url":null,"abstract":"<p><p>Neurodevelopmental disorders can have long-lasting effects, causing not only early pediatric symptoms but also a range of neurological issues throughout adulthood. West syndrome is a severe neurodevelopmental disorder marked by infantile spasms, an early symptom that typically subsides with age. However, many patients progress to other seizure forms, known as seizure evolution, which is closely linked to poor long-term outcomes. Despite its clinical significance, the neurobiological mechanisms behind seizure evolution in West syndrome remain poorly understood. Recent genetic studies have consistently identified the CYFIP2 p.Arg87Cys variant in West syndrome patients, and the Cyfip2+/R87C mouse model carrying this mutation has been shown to recapitulate key symptoms of the disorder, including infantile spasms. In this study, we aimed to gain deeper insight into seizure evolution by conducting longitudinal deep phenotyping of the Cyfip2+/R87C mouse model from the neonatal stage to seven months of age. We tracked seizure activity through behavioral and EEG recordings and employed multi-omic analyses, including tissue and single-cell level transcriptomics, ultrastructural analysis, proteomics, and lipidomics, to capture a comprehensive view of molecular and cellular changes. Our results showed that after an initial period of neonatal spasms, Cyfip2+/R87C mice entered a seizure-free phase, followed by spontaneous recurrent seizures in adulthood, ultimately leading to premature death. This progression was associated with synaptic remodeling, sequential activation of different glial cell types, lipid droplet accumulation in astrocytes, and significant proteomic and lipidomic changes in the brain. These findings suggest that seizure evolution in West syndrome involves complex, time-dependent interactions between neurons and glial cells, along with alterations in lipid metabolism. Our study highlights the potential of longitudinal multi-omic approaches to uncover underlying mechanisms of seizure evolution and suggests that targeting these changes could offer novel therapeutic strategies. Additionally, the dataset generated here may provide valuable insights for other epilepsy and neurodevelopmental disorder models.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 10","pages":"e3003192"},"PeriodicalIF":7.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145259837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2025-10-07eCollection Date: 2025-10-01DOI: 10.1371/journal.pbio.3003399
Aurore A Perrault, Valeria Kebets, Nicole M Y Kuek, Nathan E Cross, Rackeb Tesfaye, Florence B Pomares, Jingwei Li, Michael W L Chee, Thien Thanh Dang-Vu, B T Thomas Yeo
{"title":"Identification of five sleep-biopsychosocial profiles with specific neural signatures linking sleep variability with health, cognition, and lifestyle factors.","authors":"Aurore A Perrault, Valeria Kebets, Nicole M Y Kuek, Nathan E Cross, Rackeb Tesfaye, Florence B Pomares, Jingwei Li, Michael W L Chee, Thien Thanh Dang-Vu, B T Thomas Yeo","doi":"10.1371/journal.pbio.3003399","DOIUrl":"10.1371/journal.pbio.3003399","url":null,"abstract":"<p><p>Sleep is essential for optimal functioning and health. Interconnected to multiple biological, psychological, and socio-environmental factors (i.e., biopsychosocial factors), the multidimensional nature of sleep is rarely capitalized on in research. Here, we deployed a data-driven approach to identify sleep-biopsychosocial profiles that linked self-reported sleep patterns to inter-individual variability in health, cognition, and lifestyle factors in 770 healthy young adults. We uncovered five profiles, including two profiles reflecting general psychopathology associated with either reports of general poor sleep or an absence of sleep complaints (i.e., sleep resilience), respectively. The three other profiles were driven by the use of sleep aids and social satisfaction, sleep duration, and cognitive performance, and sleep disturbance linked to cognition and mental health. Furthermore, identified sleep-biopsychosocial profiles displayed unique patterns of brain network organization. In particular, somatomotor network connectivity alterations were involved in the relationships between sleep and biopsychosocial factors. These profiles can potentially untangle the interplay between individuals' variability in sleep, health, cognition, and lifestyle-equipping research and clinical settings to better support individual's well-being.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 10","pages":"e3003399"},"PeriodicalIF":7.2,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2025-10-06eCollection Date: 2025-10-01DOI: 10.1371/journal.pbio.3003407
Thomas J Stoll, Nathan D Vandjelovic, Melissa J Polonenko, Nadja R S Li, Adrian K C Lee, Ross K Maddox
{"title":"The auditory brainstem response to natural speech is not affected by selective attention.","authors":"Thomas J Stoll, Nathan D Vandjelovic, Melissa J Polonenko, Nadja R S Li, Adrian K C Lee, Ross K Maddox","doi":"10.1371/journal.pbio.3003407","DOIUrl":"10.1371/journal.pbio.3003407","url":null,"abstract":"<p><p>The ability to pick out and attend to one sound in a noisy mixture underpins successful communication in many natural scenarios. Selective attention has been shown to drastically alter sound encoding in the cortex and has been hypothesized to modulate subcortical processing via an extensive efferent network. The body of work investigating this possibility in humans has not resulted in a clear consensus, possibly owing to limitations in the available methodologies. Here, we used new experimental tools that allowed distinct neural responses from across the auditory pathway to be simultaneously acquired from human listeners attending to the sound of one person talking while ignoring a second. Our series of experiments provide convergent evidence that selective attention does not influence sound encoding in the auditory periphery or brainstem, with an effect first appearing in the cortex. Humans' ability to focus their attention on a single sound even in the presence of many others is as remarkable as it is essential. These findings add needed clarity regarding the mechanisms that make this feat possible.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 10","pages":"e3003407"},"PeriodicalIF":7.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2025-10-06DOI: 10.1371/journal.pbio.3003430
Matthew J Stower, Richard C V Tyser, Shifaan Thowfeequ, Felix Zhou, Marta Portela, Konstantinos Miti, Jacintha Sugnaseelan, Xin Lu, Shankar Srinivas
{"title":"Calcium signaling is required for anterior patterning in the mouse embryo.","authors":"Matthew J Stower, Richard C V Tyser, Shifaan Thowfeequ, Felix Zhou, Marta Portela, Konstantinos Miti, Jacintha Sugnaseelan, Xin Lu, Shankar Srinivas","doi":"10.1371/journal.pbio.3003430","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003430","url":null,"abstract":"<p><p>Anterior-posterior axis formation in the mouse embryo requires the active migration of the DVE cell population at E5.5. While intracellular Ca2+ signaling has been shown to control cell migration in multiple cell contexts, it is unknown whether it is required for DVE migration. The pattern of Ca2+ activity in the mouse embryo at early peri-implantation stages is also unknown. Using the GCaMP6f Ca2+ reporter line, we performed a detailed assessment of Ca2+ dynamics between E0.5 and E5.5 using live imaging. We find that prior to implantation, Ca2+ transients are rare, but at E5.5 widespread, periodic, Ca2+ transients in extraembryonic tissues can be observed, including in the VE and ExE. In contrast, cells of the E5.5 epiblast remain relatively quiescent but show sporadic large-scale multicellular waves. Inhibition of SERCA at E5.5 abolishes Ca2+ transients and leads to DVE arrest, indicative that these transients are required for axial patterning. Together, these results reveal the pattern of Ca2+ handling in the early mouse embryo and a novel requirement in anterior-posterior axis formation.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 10","pages":"e3003430"},"PeriodicalIF":7.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2025-10-03eCollection Date: 2025-10-01DOI: 10.1371/journal.pbio.3003417
Marco A Coelho, Márcia David-Palma, Seonju Marincowitz, Janneke Aylward, Nam Q Pham, Andrey M Yurkov, Brenda D Wingfield, Michael J Wingfield, Sheng Sun, Joseph Heitman
{"title":"The complex evolution and genomic dynamics of mating-type loci in Cryptococcus and Kwoniella.","authors":"Marco A Coelho, Márcia David-Palma, Seonju Marincowitz, Janneke Aylward, Nam Q Pham, Andrey M Yurkov, Brenda D Wingfield, Michael J Wingfield, Sheng Sun, Joseph Heitman","doi":"10.1371/journal.pbio.3003417","DOIUrl":"10.1371/journal.pbio.3003417","url":null,"abstract":"<p><p>Sexual reproduction in basidiomycete fungi is governed by MAT loci (P/R and HD), which exhibit remarkable evolutionary plasticity, characterized by expansions, rearrangements, and gene losses often associated with mating system transitions. The sister genera Cryptococcus and Kwoniella provide a powerful framework for studying MAT loci evolution owing to their diverse reproductive strategies and distinct architectures, spanning bipolar and tetrapolar systems with either linked or unlinked MAT loci. Building on recent comparative genomic analyses, we generated additional chromosome-level assemblies, uncovering distinct trajectories shaping MAT loci organization. Contrasting with the small-scale expansions and gene acquisitions observed in Kwoniella, our analyses revealed independent expansions of the P/R locus in tetrapolar Cryptococcus, possibly driven by pheromone gene duplications. Notably, these expansions coincided with a pronounced GC-content reduction best explained by reduced GC-biased gene conversion following recombination suppression, rather than relaxed codon usage selection. Diverse modes of MAT locus linkage were also identified, including three previously unrecognized transitions: one resulting in a pseudobipolar arrangement and two leading to bipolarity. All three transitions involved translocations. In the pseudobipolar configuration, the P/R and HD loci remained on the same chromosome but genetically unlinked, whereas the bipolar transitions additionally featured rearrangements that fused the two loci into a nonrecombining region. Mating assays confirmed a sexual cycle in Cryptococcus decagattii, demonstrating its ability to undergo mating and sporulation. Progeny analysis in Kwoniella mangrovensis revealed substantial ploidy variation and aneuploidy, likely stemming from haploid-diploid mating, yet evidence of recombination and loss of heterozygosity indicates that meiotic exchange occurs despite irregular chromosome segregation. Our findings underscore the importance of continued diversity sampling and provide further evidence for convergent evolution of fused MAT loci in basidiomycetes, offering new insights into the genetic and chromosomal changes driving reproductive transitions.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 10","pages":"e3003417"},"PeriodicalIF":7.2,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12510652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nicotine induces abnormal motor coupling through sensitization of a mechanosensory circuit in Caenorhabditis elegans.","authors":"Yuting Liu, Leiru Huang, Ruipeng Wang, Fukang Qi, Yiwen Liu, Qingyuan Chen, Morgane Mialon, Lili Chen, Berangere Pinan-Lucarre, Shangbang Gao","doi":"10.1371/journal.pbio.3003423","DOIUrl":"10.1371/journal.pbio.3003423","url":null,"abstract":"<p><p>Nicotine exposure elicits diverse behavioral changes, yet the underlying neural pathways and molecular mechanisms remain incompletely understood. Here, we demonstrate that chronic nicotine exposure markedly increases both the initiation and duration of reversals in Caenorhabditis elegans. Strikingly, these reversals were tightly coupled with the rhythmic body contractions of the defecation motor program (DMP). Through pharmacological, genetic, in situ electrophysiological, and calcium imaging analyses, we show that nicotine enhances the activity of the AVA interneuron via selective upregulation of ACR-16, a nicotinic ACh receptor critical for nicotine-induced motor coupling. Ablation of touch receptor neurons (TRNs) or inhibition of TRNs-mediated mechanosensation completely abolished this coupling. Furthermore, optogenetic activation of TRNs in nicotine-treated animals evoked stronger AVA depolarization, and nicotine amplified gentle touch-evoked reversals. Together, these findings reveal a potential interoceptive effect of nicotine mediated by sensitization of the TRNs-AVA mechanosensory pathway, providing new insight into the neural and molecular basis of nicotine's modulation of sensory-motor coupling.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 10","pages":"e3003423"},"PeriodicalIF":7.2,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2025-10-03eCollection Date: 2025-10-01DOI: 10.1371/journal.pbio.3003389
Ashley M Ingiosi
{"title":"Astrocytes serve as integrative hubs regulating sleep and arousal.","authors":"Ashley M Ingiosi","doi":"10.1371/journal.pbio.3003389","DOIUrl":"10.1371/journal.pbio.3003389","url":null,"abstract":"<p><p>Astrocytes help control sleep and arousal. A new study in PLOS Biology shows that a wake-promoting signal called histamine affects how astrocytes respond to and modulate other brain signals and reduces time spent awake through astroglial histamine-1-receptors.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 10","pages":"e3003389"},"PeriodicalIF":7.2,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2025-10-02eCollection Date: 2025-10-01DOI: 10.1371/journal.pbio.3003376
Charlotte R Taylor, Vincent Tse, Drew D Willoughby, Maxine Levesque, Trisha V Vaidyanathan, Jeanne T Paz, Kira E Poskanzer
{"title":"Cortical astrocyte histamine-1-receptors regulate intracellular calcium and extracellular adenosine dynamics across sleep and wake.","authors":"Charlotte R Taylor, Vincent Tse, Drew D Willoughby, Maxine Levesque, Trisha V Vaidyanathan, Jeanne T Paz, Kira E Poskanzer","doi":"10.1371/journal.pbio.3003376","DOIUrl":"10.1371/journal.pbio.3003376","url":null,"abstract":"<p><p>Classical neuromodulators regulate arousal states, spanning deep sleep to vigilant wakefulness, primarily by activating cortical neurons. However, cortical astrocytes also express neuromodulatory G-protein-coupled receptors (GPCRs). While astrocytic noradrenergic receptors have been shown to modulate two critical regulators of arousal-cortical synchrony and extracellular adenosine levels-how other neuromodulatory signaling pathways similarly shape arousal remains unclear. Astrocytes in mammalian cortex express particularly high levels of the wake-promoting, Gq-coupled histamine-1-receptor (H1R), yet little is known about how astrocytic H1R contributes to regulation of arousal. To address this gap, we used pharmacological and genetic approaches in murine cortex to test how astrocyte-H1R signaling affects astrocyte calcium (Ca2+), cortical neural activity across sleep/wake, and extracellular adenosine-an astrocytic output that regulates cortical arousal. Using ex vivo two-photon Ca2+ imaging in acute cortical slices, we show that H1R mediates cell-autonomous astrocyte Ca2+ responses to histamine (HA) and attenuates responses to norepinephrine (NE). Next, in vivo fiber photometry and electrophysiology results show that H1R deletion in cortical astrocytes disrupts local astrocyte Ca2+ during wake and extracellular adenosine dynamics specifically around REM sleep transitions, when HA release is minimal. Further, astrocyte-specific H1R deletion in cortex promotes wakefulness and reduces REM sleep time. Our results indicate that H1R activity modulates astrocyte responses to non-histaminergic inputs by inducing lasting changes in astrocyte physiology that modulate extracellular adenosine and REM sleep. Our findings contribute to an emerging model in which neuromodulator GPCRs synergistically shape astrocyte physiology to regulate arousal behavior and adenosine signaling in the cortex.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 10","pages":"e3003376"},"PeriodicalIF":7.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}