Neuron最新文献 - Book学术

BST2 expression at astrocyte borders promotes microglial recruitment via the C3/C3aR signaling. 星形胶质细胞边界的BST2表达通过C3/C3aR信号通路促进小胶质细胞募集。

IF 15 1区医学

Neuron Pub Date : 2025-10-24 DOI: 10.1016/j.neuron.2025.09.038

Shuang Zhang, Mengqi Yuan, Jin Zhou, Yuan Zhao, Liuyongwei Wang, Changxiong Gong, Hui Lu, Xiaofeng Cheng, Xiaoman Wang, Qian He, Linlin Hu, Bingqiao Wang, Chengkang He, Yiliang Fang, Sen Lin, Wenjie Zi, Ying He, Chenhao Zhao, Hongting Zheng, Jianqin Niu, Feng Mei, Baoliang Sun, Qi Xie, Qingwu Yang

{"title":"BST2 expression at astrocyte borders promotes microglial recruitment via the C3/C3aR signaling.","authors":"Shuang Zhang, Mengqi Yuan, Jin Zhou, Yuan Zhao, Liuyongwei Wang, Changxiong Gong, Hui Lu, Xiaofeng Cheng, Xiaoman Wang, Qian He, Linlin Hu, Bingqiao Wang, Chengkang He, Yiliang Fang, Sen Lin, Wenjie Zi, Ying He, Chenhao Zhao, Hongting Zheng, Jianqin Niu, Feng Mei, Baoliang Sun, Qi Xie, Qingwu Yang","doi":"10.1016/j.neuron.2025.09.038","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.09.038","url":null,"abstract":"Following central nervous system injury, astrocytes form borders that were traditionally regarded as physical barriers. Emerging evidence demonstrates their capacity to regulate inflammation and repair; however, the specific characteristics of these border astrocytes and their interactions with immune cells remain insufficiently characterized. Using single-cell sequencing and spatial transcriptomics, we identified astrocytes expressing the interferon-inducible protein bone marrow stromal cell antigen 2 (BST2) enriched at injury boundaries that promote microglial recruitment via C3/C3aR signaling. Astrocyte-specific Bst2 knockout reduced astrocyte-microglia interactions and attenuated border formation, correlating with early neurological improvement after stroke. Mechanistically, BST2 enhanced C3 expression through protein kinase C-βII (PKCβII) phosphorylation. Moreover, treatment with a BST2 monoclonal antibody diminished astrocyte-microglia interactions and improved neurological function. Together, these findings highlight the pivotal role of astrocyte-microglia interactions in lesion border formation and suggest that BST2 may represent a therapeutic target to modulate these interactions and reduce early brain injury after stroke.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370394","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

An enteric-DRG pathway for interoception and visceral pain in mice. 小鼠内感受和内脏疼痛的肠- drg通路。

IF 15 1区医学

Neuron Pub Date : 2025-10-23 DOI: 10.1016/j.neuron.2025.09.035

Zhuang Wang, Qihong Tang, Kai Li, Junhui Mou, Yuanyuan Chen, Wenqiong Kuang, Liting Sun, Zongya Ma, Yaru Wei, Rong Bao, Xiaohan Sun, Shaoli Wang, Wei Lu, Guang-Yin Xu, Yi-Quan Tang, Shumin Duan, Jinfei D Ni

{"title":"An enteric-DRG pathway for interoception and visceral pain in mice.","authors":"Zhuang Wang, Qihong Tang, Kai Li, Junhui Mou, Yuanyuan Chen, Wenqiong Kuang, Liting Sun, Zongya Ma, Yaru Wei, Rong Bao, Xiaohan Sun, Shaoli Wang, Wei Lu, Guang-Yin Xu, Yi-Quan Tang, Shumin Duan, Jinfei D Ni","doi":"10.1016/j.neuron.2025.09.035","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.09.035","url":null,"abstract":"Sensory afferents are major interoceptive pathways for organ-brain communication. Within the distal colon, dorsal root ganglia (DRGs) afferents regulate key gut physiology. Inflammation causes hypersensitivity of DRG pathways, leading to visceral pain. However, whether enteric neurons contribute to interoception and visceral pain remains unclear. Here, we surveyed the DRG innervation along the gastrointestinal tract in mice and found extensive associations between DRG terminals and enteric neurons. Optogenetic activation of different DRG terminals in the distal colon elicited variable degrees of behavioral responses, but only designated subpopulations induced aversion. Notably, optogenetic activation of colon cholinergic, but not nitrergic, enteric neurons signaled through the DRG-spinal pathway to evoke a non-aversive nociceptive-like reflex. Acetylcholine is part of the enteric-DRG signaling. Remarkably, inflammation shifted the nature of the enteric-DRG pathway from non-aversive to aversive. These findings expand the previous understanding of DRG-mediated visceral sensation, highlighting the contribution of enteric neuron-DRG communication to inflammation-induced visceral pain.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145368530","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

From prediction to understanding: Will AI foundation models transform brain science? 从预测到理解：人工智能基础模型会改变脑科学吗？

IF 15 1区医学

Neuron Pub Date : 2025-10-22 DOI: 10.1016/j.neuron.2025.09.039

Thomas Serre, Ellie Pavlick

引用次数: 0

Reversal of diet-induced obesity by central insulin sensitizer FSTL1. 中枢胰岛素增敏剂FSTL1逆转饮食引起的肥胖

IF 15 1区医学

Neuron Pub Date : 2025-10-21 DOI: 10.1016/j.neuron.2025.09.036

Kejia Li, Han Dai, Ke Li, Sheng Qiu, Dongfang Liu, Cong Wang, Shengbin Li, Gangyi Yang, Ling Li, Min-Dian Li, Mengliu Yang

{"title":"Reversal of diet-induced obesity by central insulin sensitizer FSTL1.","authors":"Kejia Li, Han Dai, Ke Li, Sheng Qiu, Dongfang Liu, Cong Wang, Shengbin Li, Gangyi Yang, Ling Li, Min-Dian Li, Mengliu Yang","doi":"10.1016/j.neuron.2025.09.036","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.09.036","url":null,"abstract":"Follistatin-like 1 (FSTL1) is a signaling molecule that modulates energy metabolism in peripheral tissues and is also expressed in the brain. However, whether hypothalamic FSTL1 regulates carbohydrate/lipid metabolism and energy balance remains unknown. Here, we show that FSTL1 is enriched in the hypothalamus, especially the arcuate nucleus (ARC). FSTL1 expression is decreased in diet-induced obese (DIO) and db/db mice. Agouti-related peptide (AgRP) neuron-specific Fstl1 deletion increased food intake, decreased energy expenditure, and impaired insulin sensitivity in DIO mice. Conversely, Fstl1 overexpression in AgRP neurons resulted in the opposite phenotypes. Insulin signaling was required for the anti-obesity effect of hypothalamic FSTL1. Intranasal FSTL1 delivery promoted weight loss and improved insulin sensitivity in DIO mice. Mechanistically, FSTL1 interacts with Akt, an intracellular mediator of insulin signaling, to inhibit forkhead box protein O1 (FoxO1) nuclear translocation. Our findings identify hypothalamic FSTL1 as a key mediator counteracting DIO and provide a potential pharmacological strategy for obesity-related metabolic disorders.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145346307","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

PV-dependent reorganization of prelimbic cortex sub-engrams during systems consolidation. 系统巩固过程中前额叶皮层亚印痕的pv依赖性重组。

IF 15 1区医学

Neuron Pub Date : 2025-10-20 DOI: 10.1016/j.neuron.2025.09.033

Ali Golbabaei, Sheena A Josselyn, Paul W Frankland

{"title":"PV-dependent reorganization of prelimbic cortex sub-engrams during systems consolidation.","authors":"Ali Golbabaei, Sheena A Josselyn, Paul W Frankland","doi":"10.1016/j.neuron.2025.09.033","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.09.033","url":null,"abstract":"Active ensembles of neurons form an engram during learning. However, engrams are not immutable, and their organization may change with time via systems consolidation. Here, we labeled engram ensembles in the prelimbic (PrL) cortex during contextual fear conditioning. We found that distinct engram subpopulations (\"sub-engrams\") contribute to memory recall at recent versus remote delays, with sub-engram contribution determined by their projection profile. At recent delays, sub-engrams projecting to the basal amygdala (BA) and lateral entorhinal cortex (LEC) are activated, and their activity is necessary and sufficient for memory retrieval. At remote delays, sub-engrams projecting to the nucleus reuniens (NRe) and nucleus accumbens (NAc) are additionally recruited, and their activity is necessary and sufficient for memory retrieval. Recruitment of NRe- and NAc-projecting sub-engrams to remote recall is an active process, depending on post-training activation of PrL parvalbumin-expressing interneurons. Post-training chemogenetic inhibition of PrL parvalbumin-expressing interneurons prevented sub-engram recruitment and impaired remote memory.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145346311","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

Retrotransposons unplugged: Rewiring the nervous system and wreaking havoc. 反转录转座子被拔掉：重新连接神经系统并造成严重破坏。

IF 15 1区医学

Neuron Pub Date : 2025-10-20 DOI: 10.1016/j.neuron.2025.09.034

Alexandra M Whiteley, Jason D Shepherd

引用次数: 0

Working memory readout varies with frontal theta rhythms. 工作记忆读出随额叶节奏而变化。

IF 15 1区医学

Neuron Pub Date : 2025-10-20 DOI: 10.1016/j.neuron.2025.09.031

Hio-Been Han, Scott L Brincat, Timothy J Buschman, Earl K Miller

引用次数: 0

The gain-of-function TREM2-T96K mutation increases risk for Alzheimer's disease by impairing microglial function. 功能获得性TREM2-T96K突变通过损害小胶质细胞功能增加阿尔茨海默病的风险。

IF 15 1区医学

Neuron Pub Date : 2025-10-17 DOI: 10.1016/j.neuron.2025.09.032

Dominika J Pilat, Hoang Le, Dmitry Prokopenko, Chih-Chung Jerry Lin, William A Eimer, Luisa Quinti, Evan P Gavrilles, Sheyla N Garcia, Sara N Heitman, Danielle McGinty, Murat Cetinbas, Ruslan I Sadreyev, Rudolph E Tanzi, Ana Griciuc

{"title":"The gain-of-function TREM2-T96K mutation increases risk for Alzheimer's disease by impairing microglial function.","authors":"Dominika J Pilat, Hoang Le, Dmitry Prokopenko, Chih-Chung Jerry Lin, William A Eimer, Luisa Quinti, Evan P Gavrilles, Sheyla N Garcia, Sara N Heitman, Danielle McGinty, Murat Cetinbas, Ruslan I Sadreyev, Rudolph E Tanzi, Ana Griciuc","doi":"10.1016/j.neuron.2025.09.032","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.09.032","url":null,"abstract":"We previously reported that T96K is a gain-of-function mutation in TREM2 based on its ability to increase ligand-dependent activation. Here, we show that TREM2T96K increases risk for Alzheimer's disease (AD) in a whole-genome sequencing dataset comprised of family-based and case-control samples. Trem2T96K also reduced clustering of microglia around β-amyloid (Aβ) plaques exclusively in female 5xFAD mice. Furthermore, T96K decreased levels of soluble Trem2 in female 5xFAD mice and human microglial cell cultures. We also observed impaired uptake of Aβ in Trem2T96K knockin microglial cells. Moreover, Trem2T96K reduced total area of phagocytic microglia, specifically in female 5xFAD mice. Single-cell RNA sequencing (scRNA-seq) profiling of microglia revealed that Trem2T96K impairs the transition of homeostatic microglia into disease-associated microglia (DAM) in female 5xFAD mice. Downregulated inflammatory pathways associated with Trem2T96K included interleukin (IL)-6/JAK/STAT3, complement, and interferon (IFN)-γ response. Collectively, our results indicate that, like the loss-of-function mutation R47H, Trem2T96K adversely affects microglial function in a sex-dependent manner.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318609","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

Distinct representations of economic variables across regions and projections of the frontal cortex. 经济变量跨区域和额叶皮质投影的不同表现。

IF 15 1区医学

Neuron Pub Date : 2025-10-16 DOI: 10.1016/j.neuron.2025.09.027

Antara Majumdar, Caitlin Ashcroft, Matthias Fritsche, Sandra Tan, Peter Zatka-Haas, Orsolya Folsz, Niamh Walker, Leah Mistry, Anita M Rominto, Marko Tvrdic, Zoltán Molnár, Huriye Atilgan, Adam M Packer, Simon J B Butt, Armin Lak

{"title":"Distinct representations of economic variables across regions and projections of the frontal cortex.","authors":"Antara Majumdar, Caitlin Ashcroft, Matthias Fritsche, Sandra Tan, Peter Zatka-Haas, Orsolya Folsz, Niamh Walker, Leah Mistry, Anita M Rominto, Marko Tvrdic, Zoltán Molnár, Huriye Atilgan, Adam M Packer, Simon J B Butt, Armin Lak","doi":"10.1016/j.neuron.2025.09.027","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.09.027","url":null,"abstract":"Economic decision-making requires evaluating information about available options, such as their expected value and economic risk. Previous studies have shown that frontal cortical neurons encode these variables, but how this encoding is structured across different frontal regions and projection pathways remains unclear. We developed a decision-making task for head-fixed mice in which we varied the expected value and risk associated with reward-predicting stimuli. Using large-scale electrophysiology, two-photon imaging, and projection-specific optotagging, we identified distinct spatial gradients for these variables, with stronger expected value coding in dorsal frontal regions and stronger risk coding in medial regions. We then demonstrated that this encoding further depends on the neuronal projections: frontal neurons projecting to the dorsomedial striatum and claustrum differentially encoded economic variables. Our findings illustrate that frontal cortical representation of economic variables is jointly determined by spatial organization and downstream connectivity of neurons, revealing a structured, multi-scale code for economic variables.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313390","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

Satellite glial cells: Shaping peripheral input into the brain-body axis? 卫星胶质细胞：塑造外围输入到脑-体轴？

IF 15 1区医学

Neuron Pub Date : 2025-10-15 Epub Date: 2025-06-30 DOI: 10.1016/j.neuron.2025.05.031

Pauline Meriau, Rejji Kuruvilla, Valeria Cavalli

{"title":"Satellite glial cells: Shaping peripheral input into the brain-body axis?","authors":"Pauline Meriau, Rejji Kuruvilla, Valeria Cavalli","doi":"10.1016/j.neuron.2025.05.031","DOIUrl":"10.1016/j.neuron.2025.05.031","url":null,"abstract":"Satellite glial cells (SGCs) are peripheral nervous system glial cells enveloping sensory and sympathetic ganglion neuronal soma. Traditionally viewed as mere supportive cells, recent studies reveal SGCs' dynamic role in regulating sensory and autonomic processing, positioning them to shape peripheral neural signaling. This role has the potential to impact the healthy function of numerous biological processes and contribute to disease progression. Studies now implicate peripheral sensory and autonomic deficits in the etiology of many disorders, including cognitive decline in aging, neurodevelopmental disorders, or congestive heart failure. These insights highlight SGCs' potential to influence disease processes by modulating peripheral input to the brain. This review synthesizes recent findings on SGCs, emphasizing their functions beyond metabolic support. We discuss the molecular mechanisms underlying SGCs' modulation of neuronal functions, their molecular profiles, and how these change with injury and disease. We propose that SGCs contribute to shaping peripheral input in the brain-body axis.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"3333-3351"},"PeriodicalIF":15.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144541604","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