Neuron最新文献 - Book学术

Astrocyte-mediated central amygdala microcircuit gates comorbid anxiety symptoms in chronic pain. 星形胶质细胞介导的中央杏仁核微回路门与慢性疼痛的焦虑症状共病。

IF 15 1区医学

Neuron Pub Date : 2025-10-02 DOI: 10.1016/j.neuron.2025.09.004

Gui-Ying Zan, Song-Yu Yao, Ying-Zhi Deng, Yun-Hao Jiang, Ru-Feng Ye, Yexiang Chen, Jian-Dong Long, Ying-Jie Cheng, Jing-Rui Chai, Chi Xu, Min Zhao, Zhi-Qiang Liu, Jing-Gen Liu, Yu-Jun Wang

{"title":"Astrocyte-mediated central amygdala microcircuit gates comorbid anxiety symptoms in chronic pain.","authors":"Gui-Ying Zan, Song-Yu Yao, Ying-Zhi Deng, Yun-Hao Jiang, Ru-Feng Ye, Yexiang Chen, Jian-Dong Long, Ying-Jie Cheng, Jing-Rui Chai, Chi Xu, Min Zhao, Zhi-Qiang Liu, Jing-Gen Liu, Yu-Jun Wang","doi":"10.1016/j.neuron.2025.09.004","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.09.004","url":null,"abstract":"Comorbid anxiety symptoms are prominent affective components of chronic pain, yet the central mechanisms underlying these symptoms remain elusive. The central amygdala (CeA) regulates nociceptive processing and associated anxiety in chronic pain. However, the specific microcircuits and cell types within the CeA that regulate pain-related anxiety have not been fully elucidated. In this study, we discovered a microcircuit in the CeA wherein dynorphinergic neurons of the lateral subdivision of the central amygdala (CeL) project to the medial subdivision (CeM), activation of which gates anxiogenic effects associated with chronic pain. Dynorphin-mediated activation of CeM astroglial kappa opioid receptors (KORs), dependent upon corticotropin-releasing factor (CRF) receptor 2 signaling, enhanced CeM neuron excitability by promoting N-methyl-D-aspartate receptor (NMDAR) activation, likely via releasing gliotransmitter D-serine. Behaviorally, KOR-mediated bidirectional communication between CeA peptidergic neurons and astrocytes modulates the anxiogenic effect of chronic pain. Our findings reveal a neuroglial microcircuit underlying pain-associated anxiety and suggest potential targets for therapeutic intervention.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225515","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

Hippocampal ripple diversity organizes neuronal reactivation dynamics in the offline brain. 海马体纹波多样性组织离线大脑中的神经元再激活动力学。

IF 15 1区医学

Neuron Pub Date : 2025-10-02 DOI: 10.1016/j.neuron.2025.09.012

Manfredi Castelli, Vítor Lopes-Dos-Santos, Giuseppe P Gava, Renaud Lambiotte, David Dupret

{"title":"Hippocampal ripple diversity organizes neuronal reactivation dynamics in the offline brain.","authors":"Manfredi Castelli, Vítor Lopes-Dos-Santos, Giuseppe P Gava, Renaud Lambiotte, David Dupret","doi":"10.1016/j.neuron.2025.09.012","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.09.012","url":null,"abstract":"Hippocampal ripples are highly synchronized neuronal population patterns reactivating past waking experiences in the offline brain. Whether the level, structure, and content of ripple-nested activity are consistent across consecutive events or are tuned in each event remains unclear. By profiling individual ripples using laminar currents in the mouse hippocampus during sleep/rest, we identified ripples in stratum pyramidale that feature current sinks in stratum radiatum (Radsink) versus stratum lacunosum-moleculare (LMsink). These two ripple profiles recruit neurons differently. Radsink ripples integrate recent motifs of waking coactivity, combining superficial and deep CA1 principal cells into denser, higher-dimensional patterns that undergo hour-long stable reactivation. By contrast, LMsink ripples contain core motifs of prior coactivity, engaging deep cells in sparser, lower-dimensional patterns that undergo a reactivation drift to gradually update their pre-existing content for recent wakefulness. We propose that ripple-by-ripple diversity supports parallel reactivation channels for integrating recent wakefulness while updating prior representations.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225469","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

SCOPE-C reveals long-range enhancer networks emerging as key regulators during human cortical neurogenesis. SCOPE-C揭示了在人类皮层神经发生过程中作为关键调节因子出现的远程增强网络。

IF 15 1区医学

Neuron Pub Date : 2025-10-02 DOI: 10.1016/j.neuron.2025.09.008

Lumeng Jia, Yingping Hou, Zejia Cui, Xin Luo, Jiali Duan, Jianbin Guo, Benhui You, Qing Fang, Xiaotian Wang, Minglei Shi, Hebing Chen, Fengyun Zhang, Jingyun Mo, Yujia Liao, Yujie Sun, Jia Wang, Tingting Li, Bing Su, Lan Zhu, Cheng Li

{"title":"SCOPE-C reveals long-range enhancer networks emerging as key regulators during human cortical neurogenesis.","authors":"Lumeng Jia, Yingping Hou, Zejia Cui, Xin Luo, Jiali Duan, Jianbin Guo, Benhui You, Qing Fang, Xiaotian Wang, Minglei Shi, Hebing Chen, Fengyun Zhang, Jingyun Mo, Yujia Liao, Yujie Sun, Jia Wang, Tingting Li, Bing Su, Lan Zhu, Cheng Li","doi":"10.1016/j.neuron.2025.09.008","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.09.008","url":null,"abstract":"Chromatin in the human brain cortex shows more enhancer-enhancer contacts than in macaques and mice, yet the organization of these contacts across cellular states and the mechanisms behind them remain unclear. Here, we developed simultaneous conformation and open-chromatin capture (SCOPE-C) to map open chromatin and its long-range spatial interactions from low-input samples. Applying SCOPE-C to fetal cortical cells from humans, macaques, and mice, we reveal that human neurogenesis is characterized by extended long-range (>1 megabase [Mb]) enhancer-promoter loops formed via CCCTC-binding factor (CTCF) mediated loop extrusion. In human excitatory neurons (ENs), these interactions establish dynamic networks spanning up to 10 Mb. These networks are enriched with human-biased enhancers and neuropsychiatric disorder-linked single-nucleotide polymorphisms (SNPs) regulating key cell-fate genes such as SATB2. The formation of these vast, dynamic enhancer networks appears to be a prominent feature of human ENs, offering mechanistic insights into cortical evolution and the genetic vulnerability of neurodevelopmental regulation.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225510","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

Hunger modulates exploration through suppression of dopamine signaling in the tail of the striatum. 饥饿通过抑制纹状体尾部的多巴胺信号来调节探索。

IF 15 1区医学

Neuron Pub Date : 2025-10-02 DOI: 10.1016/j.neuron.2025.09.009

Tarun Kamath, Bart Lodder, Eliana Bilsel, Isobel Green, Rochelin Dalangin, Michelle Raghubardayal, Wengang Wang, Paolo Capelli, Jessie Legister, Joshua Timmins, Lauren Hulshof, Janet Berrios Wallace, Lin Tian, Naoshige Uchida, Mitsuko Watabe-Uchida, Bernardo L Sabatini

{"title":"Hunger modulates exploration through suppression of dopamine signaling in the tail of the striatum.","authors":"Tarun Kamath, Bart Lodder, Eliana Bilsel, Isobel Green, Rochelin Dalangin, Michelle Raghubardayal, Wengang Wang, Paolo Capelli, Jessie Legister, Joshua Timmins, Lauren Hulshof, Janet Berrios Wallace, Lin Tian, Naoshige Uchida, Mitsuko Watabe-Uchida, Bernardo L Sabatini","doi":"10.1016/j.neuron.2025.09.009","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.09.009","url":null,"abstract":"Caloric depletion induces behavioral changes that help an animal find food and restore its homeostatic balance. Hunger increases exploration and risk-taking behavior, allowing an animal to forage for food despite risks; however, it is unknown which neural systems coordinate such behavioral adaptations. Here, we characterize how hunger restructures an animal's spontaneous behavior as well as its directed exploration of a novel object. We show that hunger-induced changes in exploration are accompanied by and result from the modulation of dopamine signaling in the tail of the striatum (TOS). Dopamine signaling in the TOS is in turn modulated by hunger through the activity of agouti-related peptide (AgRP) neurons, putative \"hunger neurons\" in the arcuate nucleus of the hypothalamus that are polysynaptically connected to the TOS through the lateral hypothalamus. Thus, we delineate how hypothalamic systems modulate dopaminergic circuitry to mediate changes in exploratory behavior in the hungry state.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225476","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

Targeting tumor-associated nerves enhances cancer immunotherapy. 靶向肿瘤相关神经增强癌症免疫治疗。

IF 15 1区医学

Neuron Pub Date : 2025-10-01 DOI: 10.1016/j.neuron.2025.09.005

Canhui Cao

引用次数: 0

Gut-induced alpha-Synuclein and Tau propagation initiate Parkinson's and Alzheimer's disease co-pathology and behavior impairments. 肠道诱导的α -突触核蛋白和Tau蛋白繁殖引发帕金森病和阿尔茨海默病的共同病理和行为障碍。

IF 15 1区医学

Neuron Pub Date : 2025-10-01 Epub Date: 2025-09-23 DOI: 10.1016/j.neuron.2025.09.015

Jie Xiang, Jingrong Tang, Fei Kang, Jiajun Ye, Yueying Cui, Zhentao Zhang, Jing Wang, Shengxi Wu, Keqiang Ye

引用次数: 0

Alterations in a cross-hemispheric circuit associates with novelty discrimination deficits in mouse models of neurodegeneration. 在小鼠神经变性模型中，交叉半球回路的改变与新奇辨别缺陷有关。

IF 15 1区医学

Neuron Pub Date : 2025-10-01 Epub Date: 2025-09-10 DOI: 10.1016/j.neuron.2025.09.002

Chinnakkaruppan Adaikkan, Jun Wang, Karim Abdelaal, Steven J Middleton, P Lorenzo Bozzelli, Ian R Wickersham, Thomas J McHugh, Li-Huei Tsai

引用次数: 0

Dysfunction of cortical GABAergic projection neurons as a major hallmark in a model of neuropsychiatric syndrome. 皮质gaba能投射神经元功能障碍是神经精神综合征模型的主要标志。

IF 15 1区医学

Neuron Pub Date : 2025-10-01 Epub Date: 2025-09-24 DOI: 10.1016/j.neuron.2025.08.028

Andrea Asenjo-Martinez, Katarina Dragicevic, Wen-Hsien Hou, Attila Ozsvar, Nikolaj Winther Hansen, Ulrich Pfisterer, Rasmus Rydbirk, Samuel Demharter, Bente Emma Møller, Janina Gasthaus, Irina Korshunova, Jean-François Perrier, Marco Capogna, Navneet A Vasistha, Konstantin Khodosevich

{"title":"Dysfunction of cortical GABAergic projection neurons as a major hallmark in a model of neuropsychiatric syndrome.","authors":"Andrea Asenjo-Martinez, Katarina Dragicevic, Wen-Hsien Hou, Attila Ozsvar, Nikolaj Winther Hansen, Ulrich Pfisterer, Rasmus Rydbirk, Samuel Demharter, Bente Emma Møller, Janina Gasthaus, Irina Korshunova, Jean-François Perrier, Marco Capogna, Navneet A Vasistha, Konstantin Khodosevich","doi":"10.1016/j.neuron.2025.08.028","DOIUrl":"10.1016/j.neuron.2025.08.028","url":null,"abstract":"Neuropsychiatric disorders have a strong genetic component and are linked to developmental risk factors, yet it is unclear why symptoms appear only later in life and which neuronal types contribute to brain dysfunction. We addressed these questions using a robust mouse model of a neuropsychiatric syndrome-the 15q13.3 microdeletion. Single-nucleus transcriptomics revealed the largest gene expression alterations in the somatostatin (Sst) Sst_Chodl subtype, the long-range γ-aminobutyric acid (GABAergic) projecting neurons. Despite the developmental onset of perturbations, impairments in Sst_Chodl neurons manifested only at late maturation. Calcium imaging and patch-clamp recordings unraveled impaired responsivity overall in deep-layer Sst neurons, with only the Sst_Chodl subtype exhibiting increased activity. Patch-seq analysis connected molecular changes to cellular dysfunction of Sst_Chodl neurons. Finally, microdeletion mice displayed sleep disturbances associated with impaired activity of deep-layer Sst neurons, which were rescued by chemogenetic inhibition of Sst_Chodl neurons. Our findings spotlight GABAergic projection neurons as potential vulnerable targets in neuropsychiatric disorders.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"3204-3223.e11"},"PeriodicalIF":15.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150147","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

Neuroanatomical organization of electroacupuncture in modulating gastric function in mice and humans. 电针调节小鼠和人胃功能的神经解剖学组织。

IF 15 1区医学

Neuron Pub Date : 2025-10-01 Epub Date: 2025-07-25 DOI: 10.1016/j.neuron.2025.06.023

Shun Dong, Lijuan Zhao, Jing Liu, Xuan Sha, Yi Wu, Weili Liu, Junlong Sun, Yangshuai Su, Zhidi Zhuang, Jian Chen, Ying Dong, Beijing Xie, Anqi Zhou, Hongyan Ji, Yuchun Wang, Xiaoman Deng, Xianghong Jing, Qiufu Ma, Nianhong Wang, Shenbin Liu

{"title":"Neuroanatomical organization of electroacupuncture in modulating gastric function in mice and humans.","authors":"Shun Dong, Lijuan Zhao, Jing Liu, Xuan Sha, Yi Wu, Weili Liu, Junlong Sun, Yangshuai Su, Zhidi Zhuang, Jian Chen, Ying Dong, Beijing Xie, Anqi Zhou, Hongyan Ji, Yuchun Wang, Xiaoman Deng, Xianghong Jing, Qiufu Ma, Nianhong Wang, Shenbin Liu","doi":"10.1016/j.neuron.2025.06.023","DOIUrl":"10.1016/j.neuron.2025.06.023","url":null,"abstract":"Somatosensory-vagal reflexes evoked by electroacupuncture (EA) can modulate visceral functions. However, the underlying principles and neural mechanisms remain poorly understood, hindering further optimization. Here, we identified key neural components essential for EA topographically driving the somatosensory-vagal-gastric reflex in mice. EA drove this reflex via activation of a subset of transient receptor potential vanilloid-1 (TRPV1)+ nociceptors marked by the expression of Adra2a and located exclusively in deep fascial tissues. Through TRPV1+ fibers, EA activated a subtype of gastro-projecting Oxtr+ fibers originating from the dorsal motor nucleus of the vagus (DMV). Genetic ablation of TRPV1+ fibers or Oxtr+ DMV neurons attenuated EA-induced gastric reflexes. Conversely, optogenetic activation of these neurons was sufficient to drive gastric motility in mice. Using similar stimulation parameters, we demonstrated that EA successfully improved gastric functions in patients with dysmotility-like functional dyspepsia (chictr.org.cn: ChiCTR2300072636). Our findings thus provide a neural anatomical basis for EA topographically to promote and treat gastric motility disorders.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"3243-3259.e11"},"PeriodicalIF":15.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718175","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 genetic predisposition to mental health: Human cortical development in vitro. 从遗传易感性到心理健康：体外人类皮质发育

IF 15 1区医学

Neuron Pub Date : 2025-10-01 DOI: 10.1016/j.neuron.2025.08.025

Arghya Mukherjee, Pico Caroni

引用次数: 0