PLoS BiologyPub Date : 2024-10-14eCollection Date: 2024-10-01DOI: 10.1371/journal.pbio.3002814
Fanny Mazzamurro, Jason Baby Chirakadavil, Isabelle Durieux, Ludovic Poiré, Julie Plantade, Christophe Ginevra, Sophie Jarraud, Gottfried Wilharm, Xavier Charpentier, Eduardo P C Rocha
{"title":"Intragenomic conflicts with plasmids and chromosomal mobile genetic elements drive the evolution of natural transformation within species.","authors":"Fanny Mazzamurro, Jason Baby Chirakadavil, Isabelle Durieux, Ludovic Poiré, Julie Plantade, Christophe Ginevra, Sophie Jarraud, Gottfried Wilharm, Xavier Charpentier, Eduardo P C Rocha","doi":"10.1371/journal.pbio.3002814","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002814","url":null,"abstract":"<p><p>Natural transformation is the only mechanism of genetic exchange controlled by the recipient bacteria. We quantified its rates in 786 clinical strains of the human pathogens Legionella pneumophila (Lp) and 496 clinical and environmental strains of Acinetobacter baumannii (Ab). The analysis of transformation rates in the light of phylogeny revealed they evolve by a mixture of frequent small changes and a few large quick jumps across 6 orders of magnitude. In standard conditions close to half of the strains of Lp and a more than a third in Ab are below the detection limit and thus presumably non-transformable. Ab environmental strains tend to have higher transformation rates than the clinical ones. Transitions to non-transformability were frequent and usually recent, suggesting that they are deleterious and subsequently purged by natural selection. Accordingly, we find that transformation decreases genetic linkage in both species, which might accelerate adaptation. Intragenomic conflicts with chromosomal mobile genetic elements (MGEs) and plasmids could explain these transitions and a GWAS confirmed systematic negative associations between transformation and MGEs: plasmids and other conjugative elements in Lp, prophages in Ab, and transposable elements in both. In accordance with the hypothesis of modulation of transformation rates by genetic conflicts, transformable strains have fewer MGEs in both species and some MGEs inactivate genes implicated in the transformation with heterologous DNA (in Ab). Innate defense systems against MGEs are associated with lower transformation rates, especially restriction-modification systems. In contrast, CRISPR-Cas systems are associated with higher transformation rates suggesting that adaptive defense systems may facilitate cell protection from MGEs while preserving genetic exchanges by natural transformation. Ab and Lp have different lifestyles, gene repertoires, and population structure. Nevertheless, they exhibit similar trends in terms of variation of transformation rates and its determinants, suggesting that genetic conflicts could drive the evolution of natural transformation in many bacteria.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478511","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 : 2024-10-09eCollection Date: 2024-10-01DOI: 10.1371/journal.pbio.3002847
Joshua G Schraiber, Michael D Edge, Matt Pennell
{"title":"Unifying approaches from statistical genetics and phylogenetics for mapping phenotypes in structured populations.","authors":"Joshua G Schraiber, Michael D Edge, Matt Pennell","doi":"10.1371/journal.pbio.3002847","DOIUrl":"10.1371/journal.pbio.3002847","url":null,"abstract":"<p><p>In both statistical genetics and phylogenetics, a major goal is to identify correlations between genetic loci or other aspects of the phenotype or environment and a focal trait. In these 2 fields, there are sophisticated but disparate statistical traditions aimed at these tasks. The disconnect between their respective approaches is becoming untenable as questions in medicine, conservation biology, and evolutionary biology increasingly rely on integrating data from within and among species, and once-clear conceptual divisions are becoming increasingly blurred. To help bridge this divide, we lay out a general model describing the covariance between the genetic contributions to the quantitative phenotypes of different individuals. Taking this approach shows that standard models in both statistical genetics (e.g., genome-wide association studies; GWAS) and phylogenetic comparative biology (e.g., phylogenetic regression) can be interpreted as special cases of this more general quantitative-genetic model. The fact that these models share the same core architecture means that we can build a unified understanding of the strengths and limitations of different methods for controlling for genetic structure when testing for associations. We develop intuition for why and when spurious correlations may occur analytically and conduct population-genetic and phylogenetic simulations of quantitative traits. The structural similarity of problems in statistical genetics and phylogenetics enables us to take methodological advances from one field and apply them in the other. We demonstrate by showing how a standard GWAS technique-including both the genetic relatedness matrix (GRM) as well as its leading eigenvectors, corresponding to the principal components of the genotype matrix, in a regression model-can mitigate spurious correlations in phylogenetic analyses. As a case study, we re-examine an analysis testing for coevolution of expression levels between genes across a fungal phylogeny and show that including eigenvectors of the covariance matrix as covariates decreases the false positive rate while simultaneously increasing the true positive rate. More generally, this work provides a foundation for more integrative approaches for understanding the genetic architecture of phenotypes and how evolutionary processes shape it.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394560","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 : 2024-10-08eCollection Date: 2024-10-01DOI: 10.1371/journal.pbio.3002797
Ana María Triana, Juha Salmi, Nicholas Mark Edward Alexander Hayward, Jari Saramäki, Enrico Glerean
{"title":"Longitudinal single-subject neuroimaging study reveals effects of daily environmental, physiological, and lifestyle factors on functional brain connectivity.","authors":"Ana María Triana, Juha Salmi, Nicholas Mark Edward Alexander Hayward, Jari Saramäki, Enrico Glerean","doi":"10.1371/journal.pbio.3002797","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002797","url":null,"abstract":"<p><p>Our behavior and mental states are constantly shaped by our environment and experiences. However, little is known about the response of brain functional connectivity to environmental, physiological, and behavioral changes on different timescales, from days to months. This gives rise to an urgent need for longitudinal studies that collect high-frequency data. To this end, for a single subject, we collected 133 days of behavioral data with smartphones and wearables and performed 30 functional magnetic resonance imaging (fMRI) scans measuring attention, memory, resting state, and the effects of naturalistic stimuli. We find traces of past behavior and physiology in brain connectivity that extend up as far as 15 days. While sleep and physical activity relate to brain connectivity during cognitively demanding tasks, heart rate variability and respiration rate are more relevant for resting-state connectivity and movie-watching. This unique data set is openly accessible, offering an exceptional opportunity for further discoveries. Our results demonstrate that we should not study brain connectivity in isolation, but rather acknowledge its interdependence with the dynamics of the environment, changes in lifestyle, and short-term fluctuations such as transient illnesses or restless sleep. These results reflect a prolonged and sustained relationship between external factors and neural processes. Overall, precision mapping designs such as the one employed here can help to better understand intraindividual variability, which may explain some of the observed heterogeneity in fMRI findings. The integration of brain connectivity, physiology data and environmental cues will propel future environmental neuroscience research and support precision healthcare.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394558","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 : 2024-10-08eCollection Date: 2024-10-01DOI: 10.1371/journal.pbio.3002818
Yi Luo, Terry Lohrenz, Ellen A Lumpkin, P Read Montague, Kenneth T Kishida
{"title":"The expectations humans have of a pleasurable sensation asymmetrically shape neuronal responses and subjective experiences to hot sauce.","authors":"Yi Luo, Terry Lohrenz, Ellen A Lumpkin, P Read Montague, Kenneth T Kishida","doi":"10.1371/journal.pbio.3002818","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002818","url":null,"abstract":"<p><p>Expectations shape our perception, profoundly influencing how we interpret the world. Positive expectations about sensory stimuli can alleviate distress and reduce pain (e.g., placebo effect), while negative expectations may heighten anxiety and exacerbate pain (e.g., nocebo effect). To investigate the impact of the (an)hedonic aspect of expectations on subjective experiences, we measured neurobehavioral responses to the taste of hot sauce among participants with heterogeneous taste preferences. By identifying participants who \"liked\" versus those who strongly \"disliked\" spicy flavors and by providing contextual cues about the spiciness of the sauce to be tasted, we dissociated the effects of positive and negative expectations from sensory stimuli (i.e., visual and gustatory stimuli), which were the same across all participants. Our results indicate that positive expectations lead to modulations in the intensity of subjective experience. These modulations were accompanied by increased activity in brain regions previously linked to information integration and the placebo effect, including the anterior insula, dorsolateral prefrontal cortex, and dorsal anterior cingulate cortex, as well as a predefined \"pleasure signature.\" In contrast, negative expectations decreased hedonic experience and increased neural activity in the previously validated \"Neurological Pain Signature\" network. These findings demonstrate that hedonic aspects of one's expectations asymmetrically shape how the brain processes sensory input and associated behavioral reports of one's subjective experiences of intensity, pleasure, and pain. Our results suggest a dissociable impact of hedonic information: positive expectations facilitate higher-level information integration and reward processing, while negative expectations prime lower-level nociceptive and affective processes. This study demonstrates the powerful role of hedonic expectations in shaping subjective reality and suggests potential avenues for consumer and therapeutic interventions targeting expectation-driven neural processes.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394559","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":"Amalgam plays a dual role in controlling the number of leg muscle progenitors and regulating their interactions with the developing Drosophila tendon.","authors":"Blandine Moucaud, Elodie Prince, Elia Ragot, Yoan Renaud, Krzysztof Jagla, Guillaume Junion, Cedric Soler","doi":"10.1371/journal.pbio.3002842","DOIUrl":"10.1371/journal.pbio.3002842","url":null,"abstract":"<p><p>Formation of functional organs requires cell-cell communication between different cell lineages and failure in this communication can result in severe developmental defects. Hundreds of possible interacting pairs of proteins are known, but identifying the interacting partners that ensure a specific interaction between 2 given cell types remains challenging. Here, we use the Drosophila leg model and our cell type-specific transcriptomic data sets to uncover the molecular mediators of cell-cell communication between tendon and muscle precursors. Through the analysis of gene expression signatures of appendicular muscle and tendon precursor cells, we identify 2 candidates for early interactions between these 2 cell populations: Amalgam (Ama) encoding a secreted protein and Neurotactin (Nrt) known to encode a membrane-bound protein. Developmental expression and function analyses reveal that: (i) Ama is expressed in the leg myoblasts, whereas Nrt is expressed in adjacent tendon precursors; and (ii) in Ama and Nrt mutants, myoblast-tendon cell-cell association is lost, leading to tendon developmental defects. Furthermore, we demonstrate that Ama acts downstream of the FGFR pathway to maintain the myoblast population by promoting cell survival and proliferation in an Nrt-independent manner. Together, our data pinpoint Ama and Nrt as molecular actors ensuring early reciprocal communication between leg muscle and tendon precursors, a prerequisite for the coordinated development of the appendicular musculoskeletal system.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11486429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394557","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 : 2024-10-04eCollection Date: 2024-10-01DOI: 10.1371/journal.pbio.3002826
Gaurav Baruah, Meike J Wittmann
{"title":"Reviving collapsed plant-pollinator networks from a single species.","authors":"Gaurav Baruah, Meike J Wittmann","doi":"10.1371/journal.pbio.3002826","DOIUrl":"10.1371/journal.pbio.3002826","url":null,"abstract":"<p><p>Mutualistic ecological networks can suddenly transition to undesirable states due to small changes in environmental conditions. Recovering from such a collapse can be difficult as restoring the original environmental conditions may be infeasible. Additionally, such networks can also exhibit a phenomenon known as hysteresis, whereby the system could exhibit multiple states under the same environmental conditions, implying that ecological networks may not recover. Here, we attempted to revive collapsed mutualistic networks to a high-functioning state from a single species, using concepts from signal propagation theory and an eco-evolutionary model based on network structures of 115 empirical plant-pollinator networks. We found that restoring the environmental conditions rarely aided in recovery of collapsed networks, but a positive relationship between recovering pollinator density and network nestedness emerged, which was qualitatively supported by empirical plant-pollinator restoration data. In contrast, network resurrection from a collapsed state in undesirable environmental conditions where restoration has minimal impacts could be readily achieved by perturbing a single species or a few species that control the response of the dynamical networks. Additionally, nestedness in networks and a moderate amount of trait variation could aid in the revival of networks even in undesirable environmental conditions. Our work suggests that focus should be applied to a few species whose dynamics could be steered to resurrect entire networks from a collapsed state and that network architecture could play a crucial role in reviving collapsed plant-pollinator networks.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376204","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":"Impaired motor-to-sensory transformation mediates auditory hallucinations.","authors":"Fuyin Yang, Hao Zhu, Xinyi Cao, Hui Li, Xinyu Fang, Lingfang Yu, Siqi Li, Zenan Wu, Chunbo Li, Chen Zhang, Xing Tian","doi":"10.1371/journal.pbio.3002836","DOIUrl":"10.1371/journal.pbio.3002836","url":null,"abstract":"<p><p>Distinguishing reality from hallucinations requires efficient monitoring of agency. It has been hypothesized that a copy of motor signals, termed efference copy (EC) or corollary discharge (CD), suppresses sensory responses to yield a sense of agency; impairment of the inhibitory function leads to hallucinations. However, how can the sole absence of inhibition yield positive symptoms of hallucinations? We hypothesize that selective impairments in functionally distinct signals of CD and EC during motor-to-sensory transformation cause the positive symptoms of hallucinations. In an electroencephalography (EEG) experiment with a delayed articulation paradigm in schizophrenic patients with (AVHs) and without auditory verbal hallucinations (non-AVHs), we found that preparing to speak without knowing the contents (general preparation) did not suppress auditory responses in both patient groups, suggesting the absent of inhibitory function of CD. Whereas, preparing to speak a syllable (specific preparation) enhanced the auditory responses to the prepared syllable in non-AVHs, whereas AVHs showed enhancement in responses to unprepared syllables, opposite to the observations in the normal population, suggesting that the enhancement function of EC is not precise in AVHs. A computational model with a virtual lesion of an inhibitory inter-neuron and disproportional sensitization of auditory cortices fitted the empirical data and further quantified the distinct impairments in motor-to-sensory transformation in AVHs. These results suggest that \"broken\" CD plus \"noisy\" EC causes erroneous monitoring of the imprecise generation of internal auditory representation and yields auditory hallucinations. Specific impairments in functional granularity of motor-to-sensory transformation mediate positivity symptoms of agency abnormality in mental disorders.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373299","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 : 2024-10-03eCollection Date: 2024-10-01DOI: 10.1371/journal.pbio.3002827
Suresha G Prabhu, Vineeta N Pillai, Lizna Mohamed Ali, Valérie Vivet-Boudou, Akhil Chameettachal, Serena Bernacchi, Farah Mustafa, Roland Marquet, Tahir A Rizvi
{"title":"MMTV RNA packaging requires an extended long-range interaction for productive Gag binding to packaging signals.","authors":"Suresha G Prabhu, Vineeta N Pillai, Lizna Mohamed Ali, Valérie Vivet-Boudou, Akhil Chameettachal, Serena Bernacchi, Farah Mustafa, Roland Marquet, Tahir A Rizvi","doi":"10.1371/journal.pbio.3002827","DOIUrl":"10.1371/journal.pbio.3002827","url":null,"abstract":"<p><p>The packaging of genomic RNA (gRNA) into retroviral particles relies on the specific recognition by the Gag precursor of packaging signals (Psi), which maintain a complex secondary structure through long-range interactions (LRIs). However, it remains unclear whether the binding of Gag to Psi alone is enough to promote RNA packaging and what role LRIs play in this process. Using mouse mammary tumor virus (MMTV), we investigated the effects of mutations in 4 proposed LRIs on gRNA structure and function. Our findings revealed the presence of an unsuspected extended LRI, and hSHAPE revealed that maintaining a wild-type-like Psi structure is crucial for efficient packaging. Surprisingly, filter-binding assays demonstrated that most mutants, regardless of their packaging capability, exhibited significant binding to Pr77Gag, suggesting that Gag binding to Psi is insufficient for efficient packaging. Footprinting experiments indicated that efficient RNA packaging is promoted when Pr77Gag binds to 2 specific sites within Psi, whereas binding elsewhere in Psi does not lead to efficient packaging. Taken together, our results suggest that the 3D structure of the Psi/Pr77Gag complex regulates the assembly of viral particles around gRNA, enabling effective discrimination against other viral and cellular RNAs that may also bind Gag efficiently.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373300","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":"Dog-human vocal interactions match dogs' sensory-motor tuning.","authors":"Eloïse C Déaux, Théophane Piette, Florence Gaunet, Thierry Legou, Luc Arnal, Anne-Lise Giraud","doi":"10.1371/journal.pbio.3002789","DOIUrl":"10.1371/journal.pbio.3002789","url":null,"abstract":"<p><p>Within species, vocal and auditory systems presumably coevolved to converge on a critical temporal acoustic structure that can be best produced and perceived. While dogs cannot produce articulated sounds, they respond to speech, raising the question as to whether this heterospecific receptive ability could be shaped by exposure to speech or remains bounded by their own sensorimotor capacity. Using acoustic analyses of dog vocalisations, we show that their main production rhythm is slower than the dominant (syllabic) speech rate, and that human-dog-directed speech falls halfway in between. Comparative exploration of neural (electroencephalography) and behavioural responses to speech reveals that comprehension in dogs relies on a slower speech rhythm tracking (delta) than humans' (theta), even though dogs are equally sensitive to speech content and prosody. Thus, the dog audio-motor tuning differs from humans', and we hypothesise that humans may adjust their speech rate to this shared temporal channel as means to improve communication efficacy.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367052","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 : 2024-10-01DOI: 10.1371/journal.pbio.3002822
Vanessa Kay Miller, Kendal Broadie
{"title":"Experience-dependent serotonergic signaling in glia regulates targeted synapse elimination.","authors":"Vanessa Kay Miller, Kendal Broadie","doi":"10.1371/journal.pbio.3002822","DOIUrl":"10.1371/journal.pbio.3002822","url":null,"abstract":"<p><p>The optimization of brain circuit connectivity based on initial environmental input occurs during critical periods characterized by sensory experience-dependent, temporally restricted, and transiently reversible synapse elimination. This precise, targeted synaptic pruning mechanism is mediated by glial phagocytosis. Serotonin signaling has prominent, foundational roles in the brain, but functions in glia, or in experience-dependent brain circuit synaptic connectivity remodeling, have been relatively unknown. Here, we discover that serotonergic signaling between glia is essential for olfactory experience-dependent synaptic glomerulus pruning restricted to a well-defined Drosophila critical period. We find that experience-dependent serotonin signaling is restricted to the critical period, with both (1) serotonin production and (2) 5-HT2A receptors specifically in glia, but not neurons, absolutely required for targeted synaptic glomerulus pruning. We discover that glial 5-HT2A receptor signaling limits the experience-dependent synaptic connectivity pruning in the critical period and that conditional reexpression of 5-HT2A receptors within adult glia reestablishes \"critical period-like\" experience-dependent synaptic glomerulus pruning at maturity. These results reveal an essential requirement for glial serotonergic signaling mediated by 5-HT2A receptors for experience-dependent synapse elimination.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367053","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}