Neuron最新文献_第5页

Shedding light on the α-synuclein fibril fuzzy coat. 揭示α-突触核蛋白原纤维的绒毛被毛。

IF 14.7 1区医学

Neuron Pub Date : 2025-06-04 DOI: 10.1016/j.neuron.2025.04.022

Joel C Watts

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Key-value memory in the brain. 大脑中的关键值记忆。

IF 14.7 1区医学

Neuron Pub Date : 2025-06-04 Epub Date: 2025-03-26 DOI: 10.1016/j.neuron.2025.02.029

Samuel J Gershman, Ila Fiete, Kazuki Irie

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Neurodevelopmental origins of structural and psychomotor defects in CXCR4-linked primary immunodeficiency. cxcr4相关原发性免疫缺陷的结构和精神运动缺陷的神经发育起源。

IF 14.7 1区医学

Neuron Pub Date : 2025-06-04 DOI: 10.1016/j.neuron.2025.05.016

Giulia Demenego, Sara Mancinelli, Antonella Borreca, Rosalba Olga Proce, Vanessa Aragona, Matteo Miotto, Marco Cremonesi, Laura Zucchelli, Irene Corradini, Eugene Kim, Katarina Ilic, Edoardo Fraviga, Luca Pellegrino, Raffaele Badolato, Roberto Rusconi, Davide Pozzi, Marinos Kallikourdis, Diana Cash, Michela Matteoli, Simona Lodato

{"title":"Neurodevelopmental origins of structural and psychomotor defects in CXCR4-linked primary immunodeficiency.","authors":"Giulia Demenego, Sara Mancinelli, Antonella Borreca, Rosalba Olga Proce, Vanessa Aragona, Matteo Miotto, Marco Cremonesi, Laura Zucchelli, Irene Corradini, Eugene Kim, Katarina Ilic, Edoardo Fraviga, Luca Pellegrino, Raffaele Badolato, Roberto Rusconi, Davide Pozzi, Marinos Kallikourdis, Diana Cash, Michela Matteoli, Simona Lodato","doi":"10.1016/j.neuron.2025.05.016","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.05.016","url":null,"abstract":"Inborn errors of immunity (IEI), as congenital chronic disorders, are often associated with neurobehavioral symptoms, traditionally considered secondary to patient burden. Their origin, however, has yet to be addressed. Here, we found that IEI-associated genes are expressed in neural lineages during human brain development, and in the absence of immunological challenges, IEI mutations directly impair neurodevelopmental trajectories, leading to psychomotor defects. Warts hypogammaglobulinemia immunodeficiency myelokathexis (WHIM) mice-bearing a mutation causing Cxcr4 hyperactivation-show developmental foliation defects of the cerebellum correlating with sensorimotor and affective dysfunctions, which recapitulate the alterations described in patients. WHIM cerebella single-cell profiling revealed major transcriptional deregulation in granule cell progenitors, whose aberrant proliferation and migration induce foliation and circuit defects. AMD3100 intracerebroventricular injection rescues both morphological and behavioral defects, demonstrating their brain-specific and Cxcr4-dependent origin. Collectively, our findings highlight the relevance of neurodevelopmental implications underlying psychomotor IEI manifestations, broadening our understanding of these conditions beyond immune dysfunctions.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248974","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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Divergent opioid-mediated suppression of inhibition between hippocampus and neocortex across species and development. 不同物种和发育中阿片介导的海马和新皮层抑制的差异。

IF 14.7 1区医学

Neuron Pub Date : 2025-06-04 Epub Date: 2025-03-26 DOI: 10.1016/j.neuron.2025.03.005

Adam P Caccavano, Anna Vlachos, Nadiya McLean, Sarah Kimmel, June Hoan Kim, Geoffrey Vargish, Vivek Mahadevan, Lauren Hewitt, Anthony M Rossi, Ilona Spineux, Sherry Jingjing Wu, Elisabetta Furlanis, Min Dai, Brenda Leyva Garcia, Yating Wang, Ramesh Chittajallu, Edra London, Xiaoqing Yuan, Steven Hunt, Daniel Abebe, Mark A G Eldridge, Alex C Cummins, Brendan E Hines, Anya Plotnikova, Arya Mohanty, Bruno B Averbeck, Kareem A Zaghloul, Jordane Dimidschstein, Gord Fishell, Kenneth A Pelkey, Chris J McBain

{"title":"Divergent opioid-mediated suppression of inhibition between hippocampus and neocortex across species and development.","authors":"Adam P Caccavano, Anna Vlachos, Nadiya McLean, Sarah Kimmel, June Hoan Kim, Geoffrey Vargish, Vivek Mahadevan, Lauren Hewitt, Anthony M Rossi, Ilona Spineux, Sherry Jingjing Wu, Elisabetta Furlanis, Min Dai, Brenda Leyva Garcia, Yating Wang, Ramesh Chittajallu, Edra London, Xiaoqing Yuan, Steven Hunt, Daniel Abebe, Mark A G Eldridge, Alex C Cummins, Brendan E Hines, Anya Plotnikova, Arya Mohanty, Bruno B Averbeck, Kareem A Zaghloul, Jordane Dimidschstein, Gord Fishell, Kenneth A Pelkey, Chris J McBain","doi":"10.1016/j.neuron.2025.03.005","DOIUrl":"10.1016/j.neuron.2025.03.005","url":null,"abstract":"Within adult rodent hippocampus (HPC), opioids suppress inhibitory parvalbumin-expressing interneurons (PV-INs), disinhibiting local microcircuits. However, it is unknown whether this disinhibitory motif is conserved across cortical regions, species, or development. We observed that PV-IN-mediated inhibition is robustly suppressed by opioids in HPC proper but not primary neocortex in mice and non-human primates, with spontaneous inhibitory tone in resected human tissue also following a consistent dichotomy. This hippocampal disinhibitory motif is established in early development when PV-INs and opioids regulate early population activity. Morphine pretreatment partially occludes this acute opioid-mediated suppression, with implications for the effects of opioids on hippocampal network activity important for learning and memory. Our findings demonstrate that PV-INs exhibit divergent opioid sensitivity across brain regions, which is remarkably conserved over evolution, and highlight the underappreciated role of opioids acting through immature PV-INs in shaping hippocampal development.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"1805-1822.e7"},"PeriodicalIF":14.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730946","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

The neurobiology of overeating. 暴饮暴食的神经生物学。

IF 14.7 1区医学

Neuron Pub Date : 2025-06-04 Epub Date: 2025-04-03 DOI: 10.1016/j.neuron.2025.03.010

Garret D Stuber, Valerie M Schwitzgebel, Christian Lüscher

{"title":"The neurobiology of overeating.","authors":"Garret D Stuber, Valerie M Schwitzgebel, Christian Lüscher","doi":"10.1016/j.neuron.2025.03.010","DOIUrl":"10.1016/j.neuron.2025.03.010","url":null,"abstract":"Food intake serves to maintain energy homeostasis; however, overeating can result in obesity, which is associated with serious health complications. In this review, we explore the intricate relationship between overeating, obesity, and the underlying neurobiological mechanisms. We review the homeostatic and hedonic feeding systems, highlighting the role of the hypothalamus and reward systems in controlling food intake and energy balance. Dysregulation in both these systems leads to overeating, as seen in genetic syndromes and environmental models affecting appetite regulation when consuming highly palatable food. The concept of \"food addiction\" is examined, drawing parallels to drug addiction. We discuss the cellular substrate for addiction-related behavior and current pharmacological obesity treatments-in particular, GLP-1 receptor agonists-showcasing synaptic plasticity in the context of overeating and palatable food exposure. A comprehensive model integrating insights from addiction research is proposed to guide effective interventions for maladaptive feeding behaviors. Ultimately, unraveling the neurobiological basis of overeating holds promise for addressing the pressing public health issue of obesity.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"1680-1693"},"PeriodicalIF":14.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788565","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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ILC2 instructs neural stem and progenitor cells to potentiate neurorepair after stroke. ILC2指示神经干和祖细胞增强脑卒中后的神经修复。

IF 14.7 1区医学

Neuron Pub Date : 2025-06-04 Epub Date: 2025-04-14 DOI: 10.1016/j.neuron.2025.03.014

Gaoyu Liu, Huachen Huang, Ying Wang, Yali Han, Jianye Wang, Mengxuan Shi, Pan Zhou, Chun Chen, Ying Yu, Qiang Liu, Jie Zhou

引用次数: 0

Vascular motion in the dorsal root ganglion sensed by Piezo2 in sensory neurons triggers episodic pain. 感觉神经元中Piezo2感知的背根神经节血管运动触发阵发性神经性疼痛。

IF 14.7 1区医学

Neuron Pub Date : 2025-06-04 Epub Date: 2025-03-27 DOI: 10.1016/j.neuron.2025.03.006

Wenrui Xie, Debora Denardin Lückemeyer, Katherine A Qualls, Arthur Silveira Prudente, Temugin Berta, Mingxia Gu, Judith A Strong, Xinzhong Dong, Jun-Ming Zhang

{"title":"Vascular motion in the dorsal root ganglion sensed by Piezo2 in sensory neurons triggers episodic pain.","authors":"Wenrui Xie, Debora Denardin Lückemeyer, Katherine A Qualls, Arthur Silveira Prudente, Temugin Berta, Mingxia Gu, Judith A Strong, Xinzhong Dong, Jun-Ming Zhang","doi":"10.1016/j.neuron.2025.03.006","DOIUrl":"10.1016/j.neuron.2025.03.006","url":null,"abstract":"Spontaneous pain, characterized by episodic shooting or stabbing sensations, is a major complaint among neuropathic pain patients, yet its mechanisms remain poorly understood. Recent research indicates a connection between this pain condition and \"clustered firing,\" wherein adjacent sensory neurons fire simultaneously. This study presents evidence that the triggers of spontaneous pain and clustered firing are the dynamic movements of small blood vessels within the nerve-injured sensory ganglion, along with increased blood vessel density/angiogenesis and increased number of pericytes around blood vessels. Pharmacologically or mechanically evoked myogenic vascular responses increase both spontaneous pain and clustered firing in a mouse model of neuropathic pain. The mechanoreceptor Piezo2 in sensory neurons plays a critical role in detecting blood vessel movements. An anti-VEGF monoclonal antibody that inhibits angiogenesis effectively blocks spontaneous pain and clustered firing. These findings suggest targeting Piezo2, angiogenesis, or abnormal vascular dynamics as potential therapeutic strategies for neuropathic spontaneous pain.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"1774-1788.e5"},"PeriodicalIF":14.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743202","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

Not just neurons: The diverse cellular landscape of learning and memory. 不仅仅是神经元：学习和记忆的不同细胞景观。

IF 14.7 1区医学

Neuron Pub Date : 2025-06-04 DOI: 10.1016/j.neuron.2025.05.005

Cristina M Alberini

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NeuroD1 induces microglial apoptosis and cannot induce microglia-to-neuron cross-lineage reprogramming. NeuroD1诱导小胶质细胞凋亡，不能诱导小胶质细胞到神经元的跨系重编程。

IF 14.7 1区医学

Neuron Pub Date : 2025-06-04 Epub Date: 2025-05-13 DOI: 10.1016/j.neuron.2025.05.006

Yanxia Rao, Siling Du, Baozhi Yang, Yuqing Wang, Yuxin Li, Ruofan Li, Tian Zhou, Xiangjuan Du, Yang He, Yafei Wang, Xin Zhou, Ti-Fei Yuan, Ying Mao, Bo Peng

引用次数: 0

Structural and functional basis of mechanosensitive TMEM63 channelopathies. 机械敏感性TMEM63通道病变的结构和功能基础。

IF 14.7 1区医学

Neuron Pub Date : 2025-06-02 DOI: 10.1016/j.neuron.2025.05.009

Wang Zheng, Augustus J Lowry, Harper E Smith, Jiale Xie, Shaun Rawson, Chen Wang, Jin Ou, Marcos Sotomayor, Tian-Min Fu, Huanghe Yang, Jeffrey R Holt

{"title":"Structural and functional basis of mechanosensitive TMEM63 channelopathies.","authors":"Wang Zheng, Augustus J Lowry, Harper E Smith, Jiale Xie, Shaun Rawson, Chen Wang, Jin Ou, Marcos Sotomayor, Tian-Min Fu, Huanghe Yang, Jeffrey R Holt","doi":"10.1016/j.neuron.2025.05.009","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.05.009","url":null,"abstract":"TMEM63A, -B, and -C constitute a mammalian family of mechanosensitive ion channels that are mutated in neurodevelopmental disorders. The molecular mechanisms underlying TMEM63 activation by force and the impact of disease-associated mutations have not been clarified. Here, we elucidate the structural and functional bases of a prevalent TMEM63B mutation p.V44M. We first found that TMEM63B p.V44M and the homologous TMEM63A p.V53M are gain-of-function mutations that do not enhance channel activity but instead evoke constitutive lipid scramblase activity. We then solved TMEM63A p.V53M mutant structures in both closed and lipid-open states, which revealed major rearrangements of pore-lining helices, creating a lateral cleft across the membrane. Simulation studies revealed lipid scrambling through this cleft. The structural rearrangements were triggered by disruption of a surface-proximal hydrophobic latch, a putative force-sensing module that includes a cluster of disease mutation sites. Our findings provide mechanistic insight into TMEM63 channelopathies and suggest a possible force-sensing mechanism.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248975","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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