Boyan Bonev, Castelo-Branco Gonçalo, Fei Chen, Simone Codeluppi, M. Ryan Corces, Jean Fan, Myriam Heiman, Kenneth Harris, Fumitaka Inoue, Manolis Kellis, Ariel Levine, Mo Lotfollahi, Chongyuan Luo, Kristen R. Maynard, Mor Nitzan, Vijay Ramani, Rahul Satijia, Lucas Schirmer, Yin Shen, Na Sun, Gilad S. Green, Fabian Theis, Xiao Wang, Joshua D. Welch, Ozgun Gokce, Genevieve Konopka, Shane Liddelow, Evan Macosko, Omer Bayraktar, Naomi Habib, Tomasz J. Nowakowski
{"title":"Opportunities and challenges of single-cell and spatially resolved genomics methods for neuroscience discovery","authors":"Boyan Bonev, Castelo-Branco Gonçalo, Fei Chen, Simone Codeluppi, M. Ryan Corces, Jean Fan, Myriam Heiman, Kenneth Harris, Fumitaka Inoue, Manolis Kellis, Ariel Levine, Mo Lotfollahi, Chongyuan Luo, Kristen R. Maynard, Mor Nitzan, Vijay Ramani, Rahul Satijia, Lucas Schirmer, Yin Shen, Na Sun, Gilad S. Green, Fabian Theis, Xiao Wang, Joshua D. Welch, Ozgun Gokce, Genevieve Konopka, Shane Liddelow, Evan Macosko, Omer Bayraktar, Naomi Habib, Tomasz J. Nowakowski","doi":"10.1038/s41593-024-01806-0","DOIUrl":"10.1038/s41593-024-01806-0","url":null,"abstract":"Over the past decade, single-cell genomics technologies have allowed scalable profiling of cell-type-specific features, which has substantially increased our ability to study cellular diversity and transcriptional programs in heterogeneous tissues. Yet our understanding of mechanisms of gene regulation or the rules that govern interactions between cell types is still limited. The advent of new computational pipelines and technologies, such as single-cell epigenomics and spatially resolved transcriptomics, has created opportunities to explore two new axes of biological variation: cell-intrinsic regulation of cell states and expression programs and interactions between cells. Here, we summarize the most promising and robust technologies in these areas, discuss their strengths and limitations and discuss key computational approaches for analysis of these complex datasets. We highlight how data sharing and integration, documentation, visualization and benchmarking of results contribute to transparency, reproducibility, collaboration and democratization in neuroscience, and discuss needs and opportunities for future technology development and analysis. This review provides an overview of analysis and experimental design of single-cell omics in the brain, emphasizing epigenomics and spatial omics. The authors discuss how the computational and experimental designs are interlinked, with both being guided by the biological questions.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2292-2309"},"PeriodicalIF":21.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142762972","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}
Federica Maltese, Giada Pacinelli, Anna Monai, Fabrizio Bernardi, Ana Marta Capaz, Marco Niello, Roman Walle, Noelia de Leon, Francesca Managò, Felix Leroy, Francesco Papaleo
{"title":"Self-experience of a negative event alters responses to others in similar states through prefrontal cortex CRF mechanisms","authors":"Federica Maltese, Giada Pacinelli, Anna Monai, Fabrizio Bernardi, Ana Marta Capaz, Marco Niello, Roman Walle, Noelia de Leon, Francesca Managò, Felix Leroy, Francesco Papaleo","doi":"10.1038/s41593-024-01816-y","DOIUrl":"https://doi.org/10.1038/s41593-024-01816-y","url":null,"abstract":"<p>Our own experience of emotional events influences how we approach and react to others’ emotions. Here we observe that mice exhibit divergent interindividual responses to others in stress (that is, preference or avoidance) only if they have previously experienced the same aversive event. These responses are estrus dependent in females and dominance dependent in males. Notably, silencing the expression of the corticotropin-releasing factor (CRF) within the medial prefrontal cortex (mPFC) attenuates the impact of stress self-experience on the reaction to others’ stress. In vivo microendoscopic calcium imaging revealed that mPFC CRF neurons are activated more toward others’ stress only following the same negative self-experience. Optogenetic manipulations confirmed that higher activation of mPFC CRF neurons is responsible for the switch from preference to avoidance of others in stress, but only following stress self-experience. These results provide a neurobiological substrate underlying how an individual’s emotional experience influences their approach toward others in a negative emotional state.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"199 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Simultaneous representations of the past and future","authors":"Henrietta Howells","doi":"10.1038/s41593-024-01840-y","DOIUrl":"10.1038/s41593-024-01840-y","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2269-2269"},"PeriodicalIF":21.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142762868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Parallel gut-to-brain pathways orchestrate feeding behaviors","authors":"Hongyun Wang, Runxiang Lou, Yunfeng Wang, Liufang Hao, Qiushi Wang, Rui Li, Jiayi Su, Shuhan Liu, Xiangyu Zhou, Xinwei Gao, Qianxi Hao, Zihe Chen, Yibo Xu, Chongwei Wu, Yang Zheng, Qingchun Guo, Ling Bai","doi":"10.1038/s41593-024-01828-8","DOIUrl":"https://doi.org/10.1038/s41593-024-01828-8","url":null,"abstract":"<p>The caudal nucleus of the solitary tract (cNTS) in the brainstem serves as a hub for integrating interoceptive cues from diverse sensory pathways. However, the mechanisms by which cNTS neurons transform these signals into behaviors remain debated. We analyzed 18 cNTS-Cre mouse lines and cataloged the dynamics of nine cNTS cell types during feeding. We show that <i>Th</i><sup>+</sup> cNTS neurons encode esophageal mechanical distension and transient gulp size via vagal afferent inputs, providing quick feedback regulation of ingestion speed. By contrast, <i>Gcg</i><sup>+</sup> cNTS neurons monitor intestinal nutrients and cumulative ingested calories and have long-term effects on food satiation and preference. These nutritive signals are conveyed through a portal vein–spinal ascending pathway rather than vagal sensory neurons. Our findings underscore distinctions among cNTS subtypes marked by differences in temporal dynamics, sensory modalities, associated visceral organs and ascending sensory pathways, all of which contribute to specific functions in coordinated feeding regulation.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"13 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Focus on single-cell genomics","authors":"","doi":"10.1038/s41593-024-01844-8","DOIUrl":"10.1038/s41593-024-01844-8","url":null,"abstract":"Single-cell genomics is deepening our understanding of the nervous system and shedding light on the heterogeneity of its cells. This focus issue of Nature Neuroscience celebrates recent methodological and analytical advances in single-cell genomics, highlights principles of study design, and aims to encourage collaboration between cellular, molecular and systems neuroscientists.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2263-2263"},"PeriodicalIF":21.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01844-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142762904","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}
{"title":"Enteric neurons and gut immunity","authors":"George Andrew S. Inglis","doi":"10.1038/s41593-024-01841-x","DOIUrl":"10.1038/s41593-024-01841-x","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2269-2269"},"PeriodicalIF":21.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142762950","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}
Jacqueline M. Griswold, Mayte Bonilla-Quintana, Renee Pepper, Christopher T. Lee, Sumana Raychaudhuri, Siyi Ma, Quan Gan, Sarah Syed, Cuncheng Zhu, Miriam Bell, Mitsuo Suga, Yuuki Yamaguchi, Ronan Chéreau, U. Valentin Nägerl, Graham Knott, Padmini Rangamani, Shigeki Watanabe
{"title":"Membrane mechanics dictate axonal pearls-on-a-string morphology and function","authors":"Jacqueline M. Griswold, Mayte Bonilla-Quintana, Renee Pepper, Christopher T. Lee, Sumana Raychaudhuri, Siyi Ma, Quan Gan, Sarah Syed, Cuncheng Zhu, Miriam Bell, Mitsuo Suga, Yuuki Yamaguchi, Ronan Chéreau, U. Valentin Nägerl, Graham Knott, Padmini Rangamani, Shigeki Watanabe","doi":"10.1038/s41593-024-01813-1","DOIUrl":"https://doi.org/10.1038/s41593-024-01813-1","url":null,"abstract":"<p>Axons are ultrathin membrane cables that are specialized for the conduction of action potentials. Although their diameter is variable along their length, how their morphology is determined is unclear. Here, we demonstrate that unmyelinated axons of the mouse central nervous system have nonsynaptic, nanoscopic varicosities ~200 nm in diameter repeatedly along their length interspersed with a thin cable ~60 nm in diameter like pearls-on-a-string. In silico modeling suggests that this axon nanopearling can be explained by membrane mechanical properties. Treatments disrupting membrane properties, such as hyper- or hypotonic solutions, cholesterol removal and nonmuscle myosin II inhibition, alter axon nanopearling, confirming the role of membrane mechanics in determining axon morphology. Furthermore, neuronal activity modulates plasma membrane cholesterol concentration, leading to changes in axon nanopearls and causing slowing of action potential conduction velocity. These data reveal that biophysical forces dictate axon morphology and function, and modulation of membrane mechanics likely underlies unmyelinated axonal plasticity.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"77 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Autism spectrum disorder variation as a computational trade-off via dynamic range of neuronal population responses","authors":"Oded Wertheimer, Yuval Hart","doi":"10.1038/s41593-024-01800-6","DOIUrl":"10.1038/s41593-024-01800-6","url":null,"abstract":"Individuals diagnosed with autism spectrum disorder (ASD) show neural and behavioral characteristics differing from the neurotypical population. This may stem from a computational principle that relates inference and computational dynamics to the dynamic range of neuronal population responses, reflecting the signal levels for which the system is responsive. In the present study, we showed that an increased dynamic range (IDR), indicating a gradual response of a neuronal population to changes in input, accounts for neural and behavioral variations in individuals diagnosed with ASD across diverse tasks. We validated the model with data from finger-tapping synchronization, orientation reproduction and global motion coherence tasks. We suggested that increased heterogeneity in the half-activation point of individual neurons may be the biological mechanism underlying the IDR in ASD. Taken together, this model provides a proof of concept for a new computational principle that may account for ASD and generates new testable and distinct predictions regarding its behavioral, neural and biological foundations. Individuals with autism spectrum disorder show neural patterns different from those of neurotypical individuals. Here the authors show that this variation reflects a computational trade-off between accurate encoding and fast adaptation tuned by the neural population response.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2476-2486"},"PeriodicalIF":21.2,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01800-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718339","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}
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