Cagney E. Coomer, Daria Naumova, Mustafa Talay, Bence Zolyomi, Nathaniel J. Snell, Altar Sorkaç, Jean Michel Chanchu, Ji Cheng, Ivana Roman, Jennifer Li, Drew Robson, David L. McLean, Gilad Barnea, Marnie E. Halpern
{"title":"Transsynaptic labeling and transcriptional control of zebrafish neural circuits","authors":"Cagney E. Coomer, Daria Naumova, Mustafa Talay, Bence Zolyomi, Nathaniel J. Snell, Altar Sorkaç, Jean Michel Chanchu, Ji Cheng, Ivana Roman, Jennifer Li, Drew Robson, David L. McLean, Gilad Barnea, Marnie E. Halpern","doi":"10.1038/s41593-024-01815-z","DOIUrl":"https://doi.org/10.1038/s41593-024-01815-z","url":null,"abstract":"<p>Deciphering the connectome, the ensemble of synaptic connections that underlie brain function, is a central goal of neuroscience research. Here we report the in vivo mapping of connections between presynaptic and postsynaptic partners in zebrafish, by adapting the <i>trans-</i>Tango genetic approach that was first developed for anterograde transsynaptic tracing in <i>Drosophila</i>. Neural connections were visualized between synaptic partners in larval retina, brain and spinal cord and followed over development. The specificity of labeling was corroborated by functional experiments in which optogenetic activation of presynaptic spinal cord interneurons elicited responses in known motor neuronal postsynaptic targets, as measured by <i>trans-</i>Tango-dependent expression of a genetically encoded calcium indicator or by electrophysiology. Transsynaptic signaling through <i>trans-</i>Tango reveals synaptic connections in the zebrafish nervous system, providing a valuable in vivo tool to monitor and interrogate neural circuits over time.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"59 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849011","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}
Amy L. Van Deusen, Sushanth Kumar, O. Yipkin Calhan, Sarah M. Goggin, Jiachen Shi, Corey M. Williams, Austin B. Keeler, Kristen I. Fread, Irene C. Gadani, Christopher D. Deppmann, Eli R. Zunder
{"title":"A single-cell mass cytometry-based atlas of the developing mouse brain","authors":"Amy L. Van Deusen, Sushanth Kumar, O. Yipkin Calhan, Sarah M. Goggin, Jiachen Shi, Corey M. Williams, Austin B. Keeler, Kristen I. Fread, Irene C. Gadani, Christopher D. Deppmann, Eli R. Zunder","doi":"10.1038/s41593-024-01786-1","DOIUrl":"https://doi.org/10.1038/s41593-024-01786-1","url":null,"abstract":"<p>Development of the mammalian brain requires precise molecular changes across diverse cell lineages. While single-cell RNA abundances in the developing brain have been characterized by single-cell RNA sequencing (scRNA-seq), single-cell protein abundances have not been characterized. To address this gap, we performed mass cytometry on the whole brain at embryonic day (E)11.5–E12.5 and the telencephalon, the diencephalon, the mesencephalon and the rhombencephalon at E13.5–postnatal day (P)4 from C57/BL6 mice. Using a 40-antibody panel to analyze 24,290,787 cells from two to four biological replicates per sample, we identify 85 molecularly distinct cell clusters from distinct lineages. Our analyses confirm canonical molecular pathways of neurogenesis and gliogenesis, and predict two distinct trajectories for cortical oligodendrogenesis. Differences in protein versus RNA expression from mass cytometry and scRNA-seq, validated by immunohistochemistry and RNAscope in situ hybridization (ISH), demonstrate the value of protein-level measurements for identifying functional cell states. Our findings show the utility of mass cytometry as a scalable platform for single-cell profiling of brain tissues.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"20 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841455","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":"Heat acclimation induces hypothalamic temperature sensitivity that promotes heat tolerance","authors":"","doi":"10.1038/s41593-024-01835-9","DOIUrl":"https://doi.org/10.1038/s41593-024-01835-9","url":null,"abstract":"After long-term heat exposure, a discrete group of hypothalamic neurons in the anterior ventromedial preoptic area become hyperactive and acquire temperature sensitivity. This reversible plasticity mechanism renders mice heat tolerant, meaning they can keep their body temperature within physiological limits when ambient temperatures are high.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"43 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142832164","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":"MeCP2 goes into unmethylated territories","authors":"Jun Young Sonn, Huda Y. Zoghbi","doi":"10.1038/s41593-024-01846-6","DOIUrl":"https://doi.org/10.1038/s41593-024-01846-6","url":null,"abstract":"Methyl-CpG-binding protein 2 (MeCP2) is a chromatin regulator whose loss of function causes Rett syndrome. It has been unclear how the gene-expression changes caused by loss of MeCP2 relate to the protein’s DNA-binding sites. New work uses the ‘CUT&RUN’ technique to identify DNA-binding sites that are largely devoid of methylation — a modification known to recruit MeCP2 to DNA.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"70 14 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142832163","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}
Boyan Bonev, Gonçalo Castelo-Branco, 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 Ali Bayraktar, Naomi Habib, Tomasz J. Nowakowski
{"title":"Author Correction: Opportunities and challenges of single-cell and spatially resolved genomics methods for neuroscience discovery","authors":"Boyan Bonev, Gonçalo Castelo-Branco, 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 Ali Bayraktar, Naomi Habib, Tomasz J. Nowakowski","doi":"10.1038/s41593-024-01858-2","DOIUrl":"https://doi.org/10.1038/s41593-024-01858-2","url":null,"abstract":"<p>Correction to: <i>Nature Neuroscience</i> https://doi.org/10.1038/s41593-024-01806-0, published online 3 December 2024.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"1 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825430","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}
Jiaxin Wang, Fangang Meng, Cuiping Xu, Yanyang Zhang, Kun Liang, Chunlei Han, Yuan Gao, Xinguang Yu, Zizhou Li, Xiaoyu Zeng, Jun Ni, Huixin Tan, Jiaxin Yang, Yina Ma
{"title":"Simultaneous intracranial recordings of interacting brains reveal neurocognitive dynamics of human cooperation","authors":"Jiaxin Wang, Fangang Meng, Cuiping Xu, Yanyang Zhang, Kun Liang, Chunlei Han, Yuan Gao, Xinguang Yu, Zizhou Li, Xiaoyu Zeng, Jun Ni, Huixin Tan, Jiaxin Yang, Yina Ma","doi":"10.1038/s41593-024-01824-y","DOIUrl":"https://doi.org/10.1038/s41593-024-01824-y","url":null,"abstract":"<p>Cooperative interactions profoundly shape individual and collective behaviors of social animals. Successful cooperation requires coordinated efforts by cooperators toward collective goals. However, the underlying behavioral dynamics and neuronal mechanisms within and between cooperating brains remain largely unknown. We recorded intracranial electrophysiological signals from human pairs engaged in a cooperation game. We show that teammate coordination and goal pursuit make distinct contributions to the behavioral cooperation dynamics. Increases and decreases in high-gamma activity in the temporoparietal junction (TPJ) and amygdala distinguish between establishing and maintaining cooperation and forecast transitions between these two states. High-gamma activity from distinct neuronal populations encodes teammate coordination and goal pursuit motives, with populations of TPJ neurons preferentially tracking dominant motives of different cooperation states. Across cooperating brains, high-gamma activity in the TPJ and amygdala synchronizes in a state-dependent manner that predicts how well cooperators coordinate. These findings provide fine-grained understandings of human cooperation dynamics as a state-dependent process with distinctive neurocognitive profiles of each state.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"4 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815722","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}
Samuel E. Marsh, Alec J. Walker, Tushar Kamath, Lasse Dissing-Olesen, Timothy R. Hammond, T. Yvanka de Soysa, Adam M. H. Young, Sarah Murphy, Abdulraouf Abdulraouf, Naeem Nadaf, Connor Dufort, Alicia C. Walker, Liliana E. Lucca, Velina Kozareva, Charles Vanderburg, Soyon Hong, Harry Bulstrode, Peter J. Hutchinson, Daniel J. Gaffney, David A. Hafler, Robin J. M. Franklin, Evan Z. Macosko, Beth Stevens
{"title":"Author Correction: Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain","authors":"Samuel E. Marsh, Alec J. Walker, Tushar Kamath, Lasse Dissing-Olesen, Timothy R. Hammond, T. Yvanka de Soysa, Adam M. H. Young, Sarah Murphy, Abdulraouf Abdulraouf, Naeem Nadaf, Connor Dufort, Alicia C. Walker, Liliana E. Lucca, Velina Kozareva, Charles Vanderburg, Soyon Hong, Harry Bulstrode, Peter J. Hutchinson, Daniel J. Gaffney, David A. Hafler, Robin J. M. Franklin, Evan Z. Macosko, Beth Stevens","doi":"10.1038/s41593-024-01855-5","DOIUrl":"https://doi.org/10.1038/s41593-024-01855-5","url":null,"abstract":"<p>Correction to: <i>Nature Neuroscience</i> https://doi.org/10.1038/s41593-022-01022-8, published online 8 Marcxh 2022.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"8 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820598","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}
Ayla Aksoy-Aksel, Francesco Ferraguti, Andrew Holmes, Andreas Lüthi, Ingrid Ehrlich
{"title":"Amygdala intercalated cells form an evolutionarily conserved system orchestrating brain networks","authors":"Ayla Aksoy-Aksel, Francesco Ferraguti, Andrew Holmes, Andreas Lüthi, Ingrid Ehrlich","doi":"10.1038/s41593-024-01836-8","DOIUrl":"https://doi.org/10.1038/s41593-024-01836-8","url":null,"abstract":"<p>The amygdala attributes valence and emotional salience to environmental stimuli and regulates how these stimuli affect behavior. Within the amygdala, a distinct class of evolutionarily conserved neurons form the intercalated cell (ITC) clusters, mainly located around the boundaries of the lateral and basal nuclei. Here, we review the anatomical, physiological and molecular characteristics of ITCs, and detail the organization of ITC clusters and their connectivity with one another and other brain regions. We describe how ITCs undergo experience-dependent plasticity and discuss emerging evidence demonstrating how ITCs are innervated and functionally regulated by neuromodulatory systems. We summarize recent findings showing that experience alters the balance of activity between different ITC clusters, thereby determining prevailing behavioral output. Finally, we propose a model in which ITCs form a key system for integrating divergent inputs and orchestrating brain-wide circuits to generate behavioral states attuned to current environmental circumstances and internal needs.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"39 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815739","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":"An RNA editing strategy rescues gene duplication in a mouse model of MECP2 duplication syndrome and nonhuman primates","authors":"Dong Yang, Xiaoqing Wu, Yinan Yao, Mengsi Duan, Xing Wang, Guoling Li, Aiguo Guo, Meixian Wu, Yuanhua Liu, Jin Zheng, Renxia Zhang, Tong Li, Alvin Luk, Xuan Yao, Linyu Shi, Chunlong Xu, Hui Yang","doi":"10.1038/s41593-024-01838-6","DOIUrl":"https://doi.org/10.1038/s41593-024-01838-6","url":null,"abstract":"<p>Duplication of methyl-CpG-binding protein 2 (<i>MECP2</i>) gene causes <i>MECP2</i> duplication syndrome (MDS). To normalize the duplicated <i>MECP2</i> in MDS, we developed a high-fidelity Cas13Y (hfCas13Y) system capable of targeting the <i>MECP2</i> (hfCas13Y-g<i>MECP2</i>) messenger RNA for degradation and reducing protein levels in the brain of humanized <i>MECP2</i> transgenic mice. Moreover, the intracerebroventricular adeno-associated virus (AAV) delivery of hfCas13Y-g<i>MECP2</i> in newborn or adult MDS mice restored dysregulated gene expression and improved behavior deficits. Notably, treatment with AAV9-hfCas13Y-g<i>MECP2</i> extended the median survival of <i>MECP2</i> transgenic mice from 156.5 to 226 d. Furthermore, studies with monkeys showed a single injection of AAV9-hfCas13Y-g<i>MECP2</i> was sufficient to drive robust expression of hfCas13Y in widespread brain regions, with <i>MECP2</i> knockdown efficiency reaching 52.19 ± 0.03% and significantly decreased expression of biomarker gene <i>GDF11</i>. Our results demonstrate that the RNA-targeting hfCas13Y-g<i>MECP2</i> system is an effective intervention for MDS, providing a potential strategy for treating other dosage-sensitive diseases.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"12 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809883","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}
Marta Pereira-Iglesias, Joel Maldonado-Teixido, Alejandro Melero, Joaquin Piriz, Elena Galea, Richard M. Ransohoff, Amanda Sierra
{"title":"Microglia as hunters or gatherers of brain synapses","authors":"Marta Pereira-Iglesias, Joel Maldonado-Teixido, Alejandro Melero, Joaquin Piriz, Elena Galea, Richard M. Ransohoff, Amanda Sierra","doi":"10.1038/s41593-024-01818-w","DOIUrl":"https://doi.org/10.1038/s41593-024-01818-w","url":null,"abstract":"<p>Over a decade ago, it was discovered that microglia, the brain’s immune cells, engulf synaptic material in a process named microglial pruning. This term suggests that microglia actively sculpt brain circuits by tagging and phagocytosing unwanted synapses. However, live imaging studies have yet to demonstrate how microglial synapse elimination occurs. To address this issue, we propose a new conceptual framework distinguishing between two potential mechanisms of synapse elimination, culling and scavenging. During culling, microglia may use a contractile ring to sever the neuronal plasma membrane, removing the unwanted synapse. During scavenging, synapse elimination is neuronal-driven, and the neuronal plasma membrane fission machinery sheds off synapses that are later phagocytosed by microglia. We will discuss the current limitations of studying microglial synapse elimination and evaluate evidence supporting either culling or scavenging. Discerning between these mechanisms is essential for determining the therapeutic value of phagocytosis modulators in diseases with altered brain connectivity.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"47 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804653","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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