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A line attractor encoding a persistent internal state requires neuropeptide signaling. 编码持久内部状态的线吸引子需要神经肽信号。
IF 45.5 1区 生物学
Cell Pub Date : 2024-10-17 Epub Date: 2024-08-26 DOI: 10.1016/j.cell.2024.08.015
George Mountoufaris, Aditya Nair, Bin Yang, Dong-Wook Kim, Amit Vinograd, Samuel Kim, Scott W Linderman, David J Anderson
{"title":"A line attractor encoding a persistent internal state requires neuropeptide signaling.","authors":"George Mountoufaris, Aditya Nair, Bin Yang, Dong-Wook Kim, Amit Vinograd, Samuel Kim, Scott W Linderman, David J Anderson","doi":"10.1016/j.cell.2024.08.015","DOIUrl":"10.1016/j.cell.2024.08.015","url":null,"abstract":"<p><p>Internal states drive survival behaviors, but their neural implementation is poorly understood. Recently, we identified a line attractor in the ventromedial hypothalamus (VMH) that represents a state of aggressiveness. Line attractors can be implemented by recurrent connectivity or neuromodulatory signaling, but evidence for the latter is scant. Here, we demonstrate that neuropeptidergic signaling is necessary for line attractor dynamics in this system by using cell-type-specific CRISPR-Cas9-based gene editing combined with single-cell calcium imaging. Co-disruption of receptors for oxytocin and vasopressin in adult VMH Esr1<sup>+</sup> neurons that control aggression diminished attack, reduced persistent neural activity, and eliminated line attractor dynamics while only slightly reducing overall neural activity and sex- or behavior-specific tuning. These data identify a requisite role for neuropeptidergic signaling in implementing a behaviorally relevant line attractor in mammals. Our approach should facilitate mechanistic studies in neuroscience that bridge different levels of biological function and abstraction.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":"5998-6015.e18"},"PeriodicalIF":45.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11490375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079285","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}
引用次数: 0
A conserved fertilization complex bridges sperm and egg in vertebrates 脊椎动物中连接精子和卵子的保守受精复合体
IF 64.5 1区 生物学
Cell Pub Date : 2024-10-17 DOI: 10.1016/j.cell.2024.09.035
Victoria E. Deneke, Andreas Blaha, Yonggang Lu, Johannes P. Suwita, Jonne M. Draper, Clara S. Phan, Karin Panser, Alexander Schleiffer, Laurine Jacob, Theresa Humer, Karel Stejskal, Gabriela Krssakova, Elisabeth Roitinger, Dominik Handler, Maki Kamoshita, Tyler D.R. Vance, Xinyin Wang, Joachim M. Surm, Yehu Moran, Jeffrey E. Lee, Andrea Pauli
{"title":"A conserved fertilization complex bridges sperm and egg in vertebrates","authors":"Victoria E. Deneke, Andreas Blaha, Yonggang Lu, Johannes P. Suwita, Jonne M. Draper, Clara S. Phan, Karin Panser, Alexander Schleiffer, Laurine Jacob, Theresa Humer, Karel Stejskal, Gabriela Krssakova, Elisabeth Roitinger, Dominik Handler, Maki Kamoshita, Tyler D.R. Vance, Xinyin Wang, Joachim M. Surm, Yehu Moran, Jeffrey E. Lee, Andrea Pauli","doi":"10.1016/j.cell.2024.09.035","DOIUrl":"https://doi.org/10.1016/j.cell.2024.09.035","url":null,"abstract":"Fertilization, the basis for sexual reproduction, culminates in the binding and fusion of sperm and egg. Although several proteins are known to be crucial for this process in vertebrates, the molecular mechanisms remain poorly understood. Using an AlphaFold-Multimer screen, we identified the protein Tmem81 as part of a conserved trimeric sperm complex with the essential fertilization factors Izumo1 and Spaca6. We demonstrate that Tmem81 is essential for male fertility in zebrafish and mice. In line with trimer formation, we show that Izumo1, Spaca6, and Tmem81 interact in zebrafish sperm and that the human orthologs interact <em>in vitro</em>. Notably, complex formation creates the binding site for the egg fertilization factor Bouncer in zebrafish. Together, our work presents a comprehensive model for fertilization across vertebrates, where a conserved sperm complex binds to divergent egg proteins—Bouncer in fish and JUNO in mammals—to mediate sperm-egg interaction.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"16 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142444202","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}
引用次数: 0
In search of problems 寻找问题
IF 64.5 1区 生物学
Cell Pub Date : 2024-10-17 DOI: 10.1016/j.cell.2024.09.017
Mu-ming Poo
{"title":"In search of problems","authors":"Mu-ming Poo","doi":"10.1016/j.cell.2024.09.017","DOIUrl":"https://doi.org/10.1016/j.cell.2024.09.017","url":null,"abstract":"With early training in physics, my career was marked by continuous learning and searching for interesting problems in biology. Here, I recount some key events that influenced my choices of research topics. The diversity of topics could be attributed to my own lack of a particular focus and the interests of students and postdocs who happened to join my laboratory. My scientific and educational ventures led to my extensive involvement in Chinese neuroscience and various studies in non-human primates.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"28 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142444192","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}
引用次数: 0
The expanding world of neuroscience 不断扩大的神经科学世界
IF 64.5 1区 生物学
Cell Pub Date : 2024-10-17 DOI: 10.1016/j.cell.2024.09.015
{"title":"The expanding world of neuroscience","authors":"","doi":"10.1016/j.cell.2024.09.015","DOIUrl":"https://doi.org/10.1016/j.cell.2024.09.015","url":null,"abstract":"Understanding the brain fascinates and intrigues many across the world. In this 50th Anniversary “Focus on Neuroscience” issue, we present Leading Edge content reflecting on the progress of the field, highlighting emerging topics, and paving the way toward many more years of exciting neuroscience research.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"2 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142444203","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}
引用次数: 0
Pioneering discovery and therapeutics at the brain-vascular-immune interface 在脑-血管-免疫界面上进行开拓性发现和治疗
IF 64.5 1区 生物学
Cell Pub Date : 2024-10-17 DOI: 10.1016/j.cell.2024.09.018
Katerina Akassoglou, Dimitrios Davalos, Andrew S. Mendiola, Mark A. Petersen, Jae Kyu Ryu, Christian Schachtrup, Zhaoqi Yan
{"title":"Pioneering discovery and therapeutics at the brain-vascular-immune interface","authors":"Katerina Akassoglou, Dimitrios Davalos, Andrew S. Mendiola, Mark A. Petersen, Jae Kyu Ryu, Christian Schachtrup, Zhaoqi Yan","doi":"10.1016/j.cell.2024.09.018","DOIUrl":"https://doi.org/10.1016/j.cell.2024.09.018","url":null,"abstract":"The brain-vascular-immune interface has emerged as a dynamic player in brain physiology and disease. We propose integrating vascular risk factors with genetic susceptibility as the nexus for the discovery of mechanisms and therapies for neuroinflammation, neurodegeneration, and neurorepair across polygenic neurologic diseases.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"14 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142444201","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}
引用次数: 0
Brain-body physiology: Local, reflex, and central communication 脑-体生理学：局部、反射和中枢通信
IF 64.5 1区 生物学
Cell Pub Date : 2024-10-17 DOI: 10.1016/j.cell.2024.08.050
Megan Sammons, Miranda C. Popescu, Jingyi Chi, Stephen D. Liberles, Nadine Gogolla, Asya Rolls
{"title":"Brain-body physiology: Local, reflex, and central communication","authors":"Megan Sammons, Miranda C. Popescu, Jingyi Chi, Stephen D. Liberles, Nadine Gogolla, Asya Rolls","doi":"10.1016/j.cell.2024.08.050","DOIUrl":"https://doi.org/10.1016/j.cell.2024.08.050","url":null,"abstract":"Behavior is tightly synchronized with bodily physiology. Internal needs from the body drive behavior selection, while optimal behavior performance requires a coordinated physiological response. Internal state is dynamically represented by the nervous system to influence mood and emotion, and body-brain signals also direct responses to external sensory cues, enabling the organism to adapt and pursue its goals within an ever-changing environment. In this review, we examine the anatomy and function of the brain-body connection, manifested across local, reflex, and central regulation levels. We explore these hierarchical loops in the context of the immune system, specifically through the lens of immunoception, and discuss the impact of its dysregulation on human health.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"44 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142444200","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}
引用次数: 0
Unraveling mechanisms of human brain evolution 揭示人类大脑进化的机制
IF 64.5 1区 生物学
Cell Pub Date : 2024-10-17 DOI: 10.1016/j.cell.2024.08.052
Madeline A. Lancaster
{"title":"Unraveling mechanisms of human brain evolution","authors":"Madeline A. Lancaster","doi":"10.1016/j.cell.2024.08.052","DOIUrl":"https://doi.org/10.1016/j.cell.2024.08.052","url":null,"abstract":"Evolutionary changes in human brain structure and function have enabled our specialized cognitive abilities. How these changes have come about genetically and functionally has remained an open question. However, new methods are providing a wealth of information about the genetic, epigenetic, and transcriptomic differences that set the human brain apart. Combined with <em>in vitro</em> models that allow access to developing brain tissue and the cells of our closest living relatives, the puzzle pieces are now coming together to yield a much more complete picture of what is actually unique about the human brain. The challenge now will be linking these observations and making the jump from correlation to causation. However, elegant genetic manipulations are now possible and, when combined with model systems such as organoids, will uncover a mechanistic understanding of how evolutionary changes at the genetic level have led to key differences in development and function that enable human cognition.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"59 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142444197","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}
引用次数: 0
The neuroscience of mental illness: Building toward the future 精神疾病的神经科学：面向未来
IF 64.5 1区 生物学
Cell Pub Date : 2024-10-17 DOI: 10.1016/j.cell.2024.09.028
Joshua A. Gordon, Kafui Dzirasa, Frederike H. Petzschner
{"title":"The neuroscience of mental illness: Building toward the future","authors":"Joshua A. Gordon, Kafui Dzirasa, Frederike H. Petzschner","doi":"10.1016/j.cell.2024.09.028","DOIUrl":"https://doi.org/10.1016/j.cell.2024.09.028","url":null,"abstract":"Mental illnesses arise from dysfunction in the brain. Although numerous extraneural factors influence these illnesses, ultimately, it is the science of the brain that will lead to novel therapies. Meanwhile, our understanding of this complex organ is incomplete, leading to the oft-repeated trope that neuroscience has yet to make significant contributions to the care of individuals with mental illnesses. This review seeks to counter this narrative, using specific examples of how neuroscientific advances have contributed to progress in mental health care in the past and how current achievements set the stage for further progress in the future.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"19 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142444198","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}
引用次数: 0
Future views on neuroscience and AI 对神经科学和人工智能的未来看法
IF 64.5 1区 生物学
Cell Pub Date : 2024-10-17 DOI: 10.1016/j.cell.2024.09.031
Ilana Witten, Daniel L.K. Yamins, Claudia Clopath, Matthias Bethge, Yi Zeng, Ann Kennedy, Abeba Birhane, Doris Tsao, Been Kim, Ila Fiete
{"title":"Future views on neuroscience and AI","authors":"Ilana Witten, Daniel L.K. Yamins, Claudia Clopath, Matthias Bethge, Yi Zeng, Ann Kennedy, Abeba Birhane, Doris Tsao, Been Kim, Ila Fiete","doi":"10.1016/j.cell.2024.09.031","DOIUrl":"https://doi.org/10.1016/j.cell.2024.09.031","url":null,"abstract":"The relationship between neuroscience and artificial intelligence (AI) has evolved rapidly over the past decade. These two areas of study influence and stimulate each other. We invited experts to share their perspectives on this exciting intersection, focusing on current achievements, unsolved questions, and future directions.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"25 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142444194","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}
引用次数: 0
IRE1α silences dsRNA to prevent taxane-induced pyroptosis in triple-negative breast cancer IRE1α 沉默dsRNA，防止三阴性乳腺癌发生由紫杉烷诱导的热休克
IF 64.5 1区 生物学
Cell Pub Date : 2024-10-16 DOI: 10.1016/j.cell.2024.09.032
Longyong Xu, Fanglue Peng, Qin Luo, Yao Ding, Fei Yuan, Liting Zheng, Wei He, Sophie S. Zhang, Xin Fu, Jin Liu, Ayse Sena Mutlu, Shuyue Wang, Ralf Bernd Nehring, Xingyu Li, Qianzi Tang, Catherine Li, Xiangdong Lv, Lacey E. Dobrolecki, Weijie Zhang, Dong Han, Xi Chen
{"title":"IRE1α silences dsRNA to prevent taxane-induced pyroptosis in triple-negative breast cancer","authors":"Longyong Xu, Fanglue Peng, Qin Luo, Yao Ding, Fei Yuan, Liting Zheng, Wei He, Sophie S. Zhang, Xin Fu, Jin Liu, Ayse Sena Mutlu, Shuyue Wang, Ralf Bernd Nehring, Xingyu Li, Qianzi Tang, Catherine Li, Xiangdong Lv, Lacey E. Dobrolecki, Weijie Zhang, Dong Han, Xi Chen","doi":"10.1016/j.cell.2024.09.032","DOIUrl":"https://doi.org/10.1016/j.cell.2024.09.032","url":null,"abstract":"Chemotherapy is often combined with immune checkpoint inhibitor (ICIs) to enhance immunotherapy responses. Despite the approval of chemo-immunotherapy in multiple human cancers, many immunologically cold tumors remain unresponsive. The mechanisms determining the immunogenicity of chemotherapy are elusive. Here, we identify the ER stress sensor IRE1α as a critical checkpoint that restricts the immunostimulatory effects of taxane chemotherapy and prevents the innate immune recognition of immunologically cold triple-negative breast cancer (TNBC). IRE1α RNase silences taxane-induced double-stranded RNA (dsRNA) through regulated IRE1-dependent decay (RIDD) to prevent NLRP3 inflammasome-dependent pyroptosis. Inhibition of IRE1α in <em>Trp53</em><sup><em>−/</em><em>−</em></sup> TNBC allows taxane to induce extensive dsRNAs that are sensed by ZBP1, which in turn activates NLRP3-GSDMD-mediated pyroptosis. Consequently, IRE1α RNase inhibitor plus taxane converts PD-L1-negative, ICI-unresponsive TNBC tumors into PD-L1<sup>high</sup> immunogenic tumors that are hyper-sensitive to ICI. We reveal IRE1α as a cancer cell defense mechanism that prevents taxane-induced danger signal accumulation and pyroptotic cell death.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"1 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439743","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}
引用次数: 0
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