Nature neuroscience最新文献_第7页

Astrocyte ensembles manipulated with AstroLight tune cue-motivated behavior

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-02-03 DOI: 10.1038/s41593-025-01870-0

Irene Serra, Cristina Martín-Monteagudo, Javier Sánchez Romero, Juan P. Quintanilla, Danny Ganchala, Maria-Angeles Arevalo, Jorge García-Marqués, Marta Navarrete

{"title":"Astrocyte ensembles manipulated with AstroLight tune cue-motivated behavior","authors":"Irene Serra, Cristina Martín-Monteagudo, Javier Sánchez Romero, Juan P. Quintanilla, Danny Ganchala, Maria-Angeles Arevalo, Jorge García-Marqués, Marta Navarrete","doi":"10.1038/s41593-025-01870-0","DOIUrl":"10.1038/s41593-025-01870-0","url":null,"abstract":"Astrocytes, dynamic cells crucial to brain function, have traditionally been overshadowed by the emphasis on neuronal activity in regulating behavior. Unlike neurons, which are organized into ensembles that encode different brain representations, astrocytes have long been considered a homogeneous population. This is partly because of the lack of tools available to map and manipulate specific subsets of astrocytes based on their functional activity, obscuring the extent of their specialization in circuits. Here, using AstroLight, a tool that translates astrocytic activity-mediated calcium signals into gene expression in a light-dependent manner, we have identified an astrocytic ensemble, a functionally specified subset of astrocytes that emerges upon activity during cue-motivated behaviors in the nucleus accumbens, an integrator hub in the reward system. Furthermore, through gain-of-function and loss-of-function manipulations, we demonstrate that this ensemble is essential for modulating cue–reward associations. These findings highlight the specialization of astrocytes into ensembles and their fine-tuning role in shaping salient behavior. Using the AstroLight system, the authors reveal that astrocytic ensembles in the nucleus accumbens regulate cue-motivated reward behavior, demonstrating that selective manipulation of tagged astrocytes can influence specific behavioral choices.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 3","pages":"616-626"},"PeriodicalIF":21.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077292","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}

引用次数: 0

Lynn T. Landmesser (1943–2024)

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-01-30 DOI: 10.1038/s41593-025-01879-5

Nicholas C. Spitzer, Ben W. Strowbridge

引用次数: 0

Oligodendrocytes in Alzheimer’s disease pathophysiology

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-01-29 DOI: 10.1038/s41593-025-01873-x

Shreeya Kedia, Mikael Simons

{"title":"Oligodendrocytes in Alzheimer’s disease pathophysiology","authors":"Shreeya Kedia, Mikael Simons","doi":"10.1038/s41593-025-01873-x","DOIUrl":"10.1038/s41593-025-01873-x","url":null,"abstract":"Our understanding of Alzheimer’s disease (AD) has transformed from a purely neuronal perspective to one that acknowledges the involvement of glial cells. Despite remarkable progress in unraveling the biology of microglia, astrocytes and vascular elements, the exploration of oligodendrocytes in AD is still in its early stages. Contrary to the traditional notion of oligodendrocytes as passive bystanders in AD pathology, emerging evidence indicates their active participation in and reaction to amyloid and tau pathology. Oligodendrocytes undergo a functional transition to a disease-associated state, engaging in immune modulation, stress responses and cellular survival. Far from being inert players, they appear to serve a dual role in AD pathogenesis, potentially offering defense mechanisms against pathology while also contributing to disease progression. This Review explores recent advancements in understanding the roles of oligodendrocytes and their myelin sheaths in the context of AD, shedding light on their complex interactions within the disease pathology. Emerging evidence highlights the dual role of oligodendrocytes in Alzheimer’s disease, both providing protective mechanisms against the pathology and contributing to its progression.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 3","pages":"446-456"},"PeriodicalIF":21.2,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055066","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}

引用次数: 0

The architecture of the human default mode network explored through cytoarchitecture, wiring and signal flow

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-01-28 DOI: 10.1038/s41593-024-01868-0

Casey Paquola, Margaret Garber, Stefan Frässle, Jessica Royer, Yigu Zhou, Shahin Tavakol, Raul Rodriguez-Cruces, Donna Gift Cabalo, Sofie Valk, Simon B. Eickhoff, Daniel S. Margulies, Alan Evans, Katrin Amunts, Elizabeth Jefferies, Jonathan Smallwood, Boris C. Bernhardt

{"title":"The architecture of the human default mode network explored through cytoarchitecture, wiring and signal flow","authors":"Casey Paquola, Margaret Garber, Stefan Frässle, Jessica Royer, Yigu Zhou, Shahin Tavakol, Raul Rodriguez-Cruces, Donna Gift Cabalo, Sofie Valk, Simon B. Eickhoff, Daniel S. Margulies, Alan Evans, Katrin Amunts, Elizabeth Jefferies, Jonathan Smallwood, Boris C. Bernhardt","doi":"10.1038/s41593-024-01868-0","DOIUrl":"10.1038/s41593-024-01868-0","url":null,"abstract":"The default mode network (DMN) is implicated in many aspects of complex thought and behavior. Here, we leverage postmortem histology and in vivo neuroimaging to characterize the anatomy of the DMN to better understand its role in information processing and cortical communication. Our results show that the DMN is cytoarchitecturally heterogenous, containing cytoarchitectural types that are variably specialized for unimodal, heteromodal and memory-related processing. Studying diffusion-based structural connectivity in combination with cytoarchitecture, we found the DMN contains regions receptive to input from sensory cortex and a core that is relatively insulated from environmental input. Finally, analysis of signal flow with effective connectivity models showed that the DMN is unique amongst cortical networks in balancing its output across the levels of sensory hierarchies. Together, our study establishes an anatomical foundation from which accounts of the broad role the DMN plays in human brain function and cognition can be developed. The default mode network (DMN) is implicated in cognition and behavior. Here, the authors show that the DMN is cytoarchitecturally heterogeneous, it contains regions receptive to input from the sensory cortex and a core relatively insulated from environmental input, and it uniquely balances its output across sensory hierarchies.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 3","pages":"654-664"},"PeriodicalIF":21.2,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01868-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049993","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}

引用次数: 0

Retrieval of conditioned immune response in male mice is mediated by an anterior–posterior insula circuit

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-01-27 DOI: 10.1038/s41593-024-01864-4

Haneen Kayyal, Federica Cruciani, Sailendrakumar Kolatt Chandran, Efrat Edry, Sagie Schif-Zuck, Tamar Koren, Adonis Yiannakas, Asya Rolls, Amiram Ariel, Kobi Rosenblum

{"title":"Retrieval of conditioned immune response in male mice is mediated by an anterior–posterior insula circuit","authors":"Haneen Kayyal, Federica Cruciani, Sailendrakumar Kolatt Chandran, Efrat Edry, Sagie Schif-Zuck, Tamar Koren, Adonis Yiannakas, Asya Rolls, Amiram Ariel, Kobi Rosenblum","doi":"10.1038/s41593-024-01864-4","DOIUrl":"10.1038/s41593-024-01864-4","url":null,"abstract":"To protect the body from infections, the brain has evolved the ability to coordinate behavioral and immunological responses. The conditioned immune response (CIR) is a form of Pavlovian conditioning wherein a sensory (for example, taste) stimulus, when paired with an immunomodulatory agent, evokes aversive behavior and an anticipatory immune response after re-experiencing the taste. Although taste and its valence are represented in the anterior insular cortex and immune response in the posterior insula and although the insula is pivotal for CIRs, the precise circuitry underlying CIRs remains unknown. Here, we demonstrated that a bidirectional circuit connecting the anterior and posterior (aIC–pIC) insula mediates the CIR in male mice. Retrieving the behavioral dimension of the association requires activity of aIC-to-pIC neurons, whereas modulating the anticipatory immunological dimension requires bidirectional projections. These results illuminate a mechanism by which experience shapes interactions between sensory internal representations and the immune system. Moreover, this newly described intrainsular circuit contributes to the preservation of brain-dependent immune homeostasis. The authors show that a bidirectional circuit connecting the anterior and posterior (aIC–pIC) insula mediates the conditioned immune response in male mice, illustrating a mechanism by which sensory experience affects immune function.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 3","pages":"589-601"},"PeriodicalIF":21.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044073","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}

引用次数: 0

α-Synuclein deposition in the kidney may contribute to Parkinson’s disease 肾脏α-突触核蛋白沉积可能与帕金森病有关

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-01-23 DOI: 10.1038/s41593-024-01867-1

引用次数: 0

Propagation of pathologic α-synuclein from kidney to brain may contribute to Parkinson’s disease 病理性α-突触核蛋白从肾向脑的增殖可能与帕金森病有关

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-01-23 DOI: 10.1038/s41593-024-01866-2

Xin Yuan, Shuke Nie, Yingxu Yang, Congcong Liu, Danhao Xia, Lanxia Meng, Yue Xia, Hua Su, Chun Zhang, Lihong Bu, Min Deng, Keqiang Ye, Jing Xiong, Liam Chen, Zhentao Zhang

{"title":"Propagation of pathologic α-synuclein from kidney to brain may contribute to Parkinson’s disease","authors":"Xin Yuan, Shuke Nie, Yingxu Yang, Congcong Liu, Danhao Xia, Lanxia Meng, Yue Xia, Hua Su, Chun Zhang, Lihong Bu, Min Deng, Keqiang Ye, Jing Xiong, Liam Chen, Zhentao Zhang","doi":"10.1038/s41593-024-01866-2","DOIUrl":"10.1038/s41593-024-01866-2","url":null,"abstract":"The pathogenesis of Lewy body diseases (LBDs), including Parkinson’s disease (PD), involves α-synuclein (α-Syn) aggregation that originates in peripheral organs and spreads to the brain. PD incidence is increased in individuals with chronic renal failure, but the underlying mechanisms remain unknown. Here we observed α-Syn deposits in the kidneys of patients with LBDs and in the kidney and central nervous system of individuals with end-stage renal disease without documented LBDs. In male mice, we found that the kidney removes α-Syn from the blood, which is reduced in renal failure, causing α-Syn deposition in the kidney and subsequent spread into the brain. Intrarenal injection of α-Syn fibrils induces the propagation of α-Syn pathology from the kidney to the brain, which is blocked by renal denervation. Deletion of α-Syn in blood cells alleviates pathology in α-Syn A53T transgenic mice. Thus, the kidney may act as an initiation site for pathogenic α-Syn spread, and compromised renal function may contribute to the onset of LBDs. Yuan et al. find that the kidney can serve as a site of initiation for the spread of pathological α-synuclein to the brain, contributing to the development of Parkinson’s disease (PD) and providing a mechanistic link between PD and renal dysfunction.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 3","pages":"577-588"},"PeriodicalIF":21.2,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020284","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}

引用次数: 0

Mapping the cellular etiology of schizophrenia and complex brain phenotypes 绘制精神分裂症和复杂脑表型的细胞病因图谱

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-01-20 DOI: 10.1038/s41593-024-01834-w

Laramie E. Duncan, Tayden Li, Madeleine Salem, Will Li, Leili Mortazavi, Hazal Senturk, Naghmeh Shahverdizadeh, Sam Vesuna, Hanyang Shen, Jong Yoon, Gordon Wang, Jacob Ballon, Longzhi Tan, Brandon Scott Pruett, Brian Knutson, Karl Deisseroth, William J. Giardino

{"title":"Mapping the cellular etiology of schizophrenia and complex brain phenotypes","authors":"Laramie E. Duncan, Tayden Li, Madeleine Salem, Will Li, Leili Mortazavi, Hazal Senturk, Naghmeh Shahverdizadeh, Sam Vesuna, Hanyang Shen, Jong Yoon, Gordon Wang, Jacob Ballon, Longzhi Tan, Brandon Scott Pruett, Brian Knutson, Karl Deisseroth, William J. Giardino","doi":"10.1038/s41593-024-01834-w","DOIUrl":"10.1038/s41593-024-01834-w","url":null,"abstract":"Psychiatric disorders are multifactorial and effective treatments are lacking. Probable contributing factors to the challenges in therapeutic development include the complexity of the human brain and the high polygenicity of psychiatric disorders. Combining well-powered genome-wide and brain-wide genetics and transcriptomics analyses can deepen our understanding of the etiology of psychiatric disorders. Here, we leverage two landmark resources to infer the cell types involved in the etiology of schizophrenia, other psychiatric disorders and informative comparison of brain phenotypes. We found both cortical and subcortical neuronal associations for schizophrenia, bipolar disorder and depression. These cell types included somatostatin interneurons, excitatory neurons from the retrosplenial cortex and eccentric medium spiny-like neurons from the amygdala. In contrast we found T cell and B cell associations with multiple sclerosis and microglial associations with Alzheimer’s disease. We provide a framework for a cell-type-based classification system that can lead to drug repurposing or development opportunities and personalized treatments. This work formalizes a data-driven, cellular and molecular model of complex brain disorders. Duncan and colleagues link specific human brain cell types to schizophrenia and other complex brain phenotypes, providing mechanistic insights and a cellular taxonomy for psychiatric disorders.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 2","pages":"248-258"},"PeriodicalIF":21.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01834-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989984","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}

引用次数: 0

Propagation of neuronal micronuclei regulates microglial characteristics 神经元微核的增殖调节着小胶质细胞的特性

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-01-17 DOI: 10.1038/s41593-024-01863-5

Sarasa Yano, Natsu Asami, Yusuke Kishi, Ikuko Takeda, Hikari Kubotani, Yuki Hattori, Ayako Kitazawa, Kanehiro Hayashi, Ken-ichiro Kubo, Mai Saeki, Chihiro Maeda, Chihiro Hiraki, Rin-ichiro Teruya, Takumi Taketomi, Kaito Akiyama, Tomomi Okajima-Takahashi, Ban Sato, Hiroaki Wake, Yukiko Gotoh, Kazunori Nakajima, Takeshi Ichinohe, Takeshi Nagata, Tomoki Chiba, Fuminori Tsuruta

{"title":"Propagation of neuronal micronuclei regulates microglial characteristics","authors":"Sarasa Yano, Natsu Asami, Yusuke Kishi, Ikuko Takeda, Hikari Kubotani, Yuki Hattori, Ayako Kitazawa, Kanehiro Hayashi, Ken-ichiro Kubo, Mai Saeki, Chihiro Maeda, Chihiro Hiraki, Rin-ichiro Teruya, Takumi Taketomi, Kaito Akiyama, Tomomi Okajima-Takahashi, Ban Sato, Hiroaki Wake, Yukiko Gotoh, Kazunori Nakajima, Takeshi Ichinohe, Takeshi Nagata, Tomoki Chiba, Fuminori Tsuruta","doi":"10.1038/s41593-024-01863-5","DOIUrl":"10.1038/s41593-024-01863-5","url":null,"abstract":"Microglia—resident immune cells in the central nervous system—undergo morphological and functional changes in response to signals from the local environment and mature into various homeostatic states. However, niche signals underlying microglial differentiation and maturation remain unknown. Here, we show that neuronal micronuclei (MN) transfer to microglia, which is followed by changing microglial characteristics during the postnatal period. Neurons passing through a dense region of the developing neocortex give rise to MN and release them into the extracellular space, before being incorporated into microglia and inducing morphological changes. Two-photon imaging analyses have revealed that microglia incorporating MN tend to slowly retract their processes. Loss of the cGAS gene alleviates effects on micronucleus-dependent morphological changes. Neuronal MN-harboring microglia also exhibit unique transcriptome signatures. These results demonstrate that neuronal MN serve as niche signals that transform microglia, and provide a potential mechanism for regulation of microglial characteristics in the early postnatal neocortex. Neuronal micronuclei are transferred to microglia during the early postnatal period, which leads to altered microglial morphology and transcriptomic signatures, suggesting that these micronuclei may act as mediators that control microglial characteristics.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 3","pages":"487-498"},"PeriodicalIF":21.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987662","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}

引用次数: 0

Dynamical constraints on neural population activity 神经种群活动的动态约束

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-01-17 DOI: 10.1038/s41593-024-01845-7

Emily R. Oby, Alan D. Degenhart, Erinn M. Grigsby, Asma Motiwala, Nicole T. McClain, Patrick J. Marino, Byron M. Yu, Aaron P. Batista

{"title":"Dynamical constraints on neural population activity","authors":"Emily R. Oby, Alan D. Degenhart, Erinn M. Grigsby, Asma Motiwala, Nicole T. McClain, Patrick J. Marino, Byron M. Yu, Aaron P. Batista","doi":"10.1038/s41593-024-01845-7","DOIUrl":"10.1038/s41593-024-01845-7","url":null,"abstract":"The manner in which neural activity unfolds over time is thought to be central to sensory, motor and cognitive functions in the brain. Network models have long posited that the brain’s computations involve time courses of activity that are shaped by the underlying network. A prediction from this view is that the activity time courses should be difficult to violate. We leveraged a brain–computer interface to challenge monkeys to violate the naturally occurring time courses of neural population activity that we observed in the motor cortex. This included challenging animals to traverse the natural time course of neural activity in a time-reversed manner. Animals were unable to violate the natural time courses of neural activity when directly challenged to do so. These results provide empirical support for the view that activity time courses observed in the brain indeed reflect the underlying network-level computational mechanisms that they are believed to implement. Oby, Degenhart, Grigsby and colleagues used a brain–computer interface to challenge monkeys to override their natural time courses of neural activity. They found the time courses to be highly robust, suggestive of network-level computational mechanisms.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 2","pages":"383-393"},"PeriodicalIF":21.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01845-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987673","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}

引用次数: 0