IF 15 1区医学

Neuron Pub Date : 2025-09-17 Epub Date: 2025-07-22 DOI: 10.1016/j.neuron.2025.06.016

Nora Ditzer, Ezgi Senoglu, Annika Kolodziejczyk, Theresa M Schütze, Aikaterina Nikolaidi, Karolin Küster, Katrin Sameith, Sevina Dietz, Razvan P Derihaci, Cahit Birdir, Anne Eugster, Mike O Karl, Andreas Dahl, Pauline Wimberger, Franziska Baenke, Claudia Peitzsch, Mareike Albert

{"title":"Epigenome profiling identifies H3K27me3 regulation of extracellular matrix composition in human corticogenesis.","authors":"Nora Ditzer, Ezgi Senoglu, Annika Kolodziejczyk, Theresa M Schütze, Aikaterina Nikolaidi, Karolin Küster, Katrin Sameith, Sevina Dietz, Razvan P Derihaci, Cahit Birdir, Anne Eugster, Mike O Karl, Andreas Dahl, Pauline Wimberger, Franziska Baenke, Claudia Peitzsch, Mareike Albert","doi":"10.1016/j.neuron.2025.06.016","DOIUrl":"10.1016/j.neuron.2025.06.016","url":null,"abstract":"Epigenetic mechanisms regulate gene expression programs during neurogenesis, but the extent of epigenetic remodeling during human cortical development remains unknown. Here, we characterize the epigenetic landscape of the human developing neocortex by leveraging Epi-CyTOF, a mass-cytometry-based approach for the simultaneous single-cell analysis of more than 30 epigenetic marks. We identify Polycomb repressive complex 2 (PRC2)-mediated H3K27me3 as the modification with the strongest cell-type-specific enrichment. Inhibition of PRC2 in human cortical organoids resulted in a shift of neural progenitor cell (NPC) proliferation toward differentiation. Cell-type-specific profiling of H3K27me3 identified neuronal differentiation and extracellular matrix (ECM) genes in the human neocortex. PRC2 inhibition resulted in increased production of the ECM proteins Syndecan 1 and laminin alpha 1. Overall, this study comprehensively characterizes the epigenetic state of specific neural cell types and highlights a novel role for H3K27me3 in regulating the ECM composition in the human developing neocortex.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"2927-2944.e10"},"PeriodicalIF":15.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699048","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 dendritic integration strategies control dynamics of inhibition in the neocortex. 不同的树突整合策略控制新皮层抑制的动态。

IF 15 1区医学

Neuron Pub Date : 2025-09-17 Epub Date: 2025-06-30 DOI: 10.1016/j.neuron.2025.05.029

Annunziato Morabito, Yann Zerlaut, Dhanasak Dhanasobhon, Emmanuelle Berthaux, Cibele Martins Pinho, Alexandra Tzilivaki, Gael Moneron, Laurence Cathala, Panayiota Poirazi, Alberto Bacci, David A DiGregorio, Joana Lourenço, Nelson Rebola

{"title":"Distinct dendritic integration strategies control dynamics of inhibition in the neocortex.","authors":"Annunziato Morabito, Yann Zerlaut, Dhanasak Dhanasobhon, Emmanuelle Berthaux, Cibele Martins Pinho, Alexandra Tzilivaki, Gael Moneron, Laurence Cathala, Panayiota Poirazi, Alberto Bacci, David A DiGregorio, Joana Lourenço, Nelson Rebola","doi":"10.1016/j.neuron.2025.05.029","DOIUrl":"10.1016/j.neuron.2025.05.029","url":null,"abstract":"Dendrites critically influence single-neuron computations, but their role in neocortical GABAergic interneurons (INs) remains poorly understood. We found that the two major cortical IN subtypes-somatostatin (SST)- and parvalbumin (PV)-expressing cells-use distinct strategies for distributing and integrating excitatory synaptic inputs along their dendrites. SST-INs exhibit NMDAR-dependent supralinear integration and a uniform distribution of synapses, whereas PV-INs show sublinear integration with a higher density of synapses on proximal dendrites with low NMDAR expression. Compartmental modeling revealed that, while both strategies enhance synaptic efficacy, passive integration and proximally biased inputs enable precise tracking of fast-changing signals in PV-INs, whereas NMDARs in SST-INs promote broader temporal integration, supporting sustained activity tuned to slower input variations. Consistent with these predictions, in vivo measurements showed differentially shaped dynamic visual responses in PV- and SST-INs. Therefore, the heterogeneity of dendritic mechanisms strongly influences the spatiotemporal dynamics of IN-specific inhibition in cortical circuits.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"2962-2978.e10"},"PeriodicalIF":15.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144541603","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

Identification of a neural basis for energy expenditure in the mouse arcuate hypothalamus. 小鼠弓形下丘脑能量消耗的神经基础鉴定。

IF 15 1区医学

Neuron Pub Date : 2025-09-17 DOI: 10.1016/j.neuron.2025.08.021

Ting Wang, Shuping Han, Yaxin Wang, Yaning Li, Yuxiao Li, Zhifang Xing, Shuangfeng Zhang, Yu Xia, Feipeng Zhu, Zhen-Hua Chen, Yu Zheng Li, Jingjing Wang, Mingrui Xu, Qinghua Liu, Man Jiang, Xiaohong Xu, Xiangning Li, Hui Gong, Peng Cao, Qing-Feng Wu

{"title":"Identification of a neural basis for energy expenditure in the mouse arcuate hypothalamus.","authors":"Ting Wang, Shuping Han, Yaxin Wang, Yaning Li, Yuxiao Li, Zhifang Xing, Shuangfeng Zhang, Yu Xia, Feipeng Zhu, Zhen-Hua Chen, Yu Zheng Li, Jingjing Wang, Mingrui Xu, Qinghua Liu, Man Jiang, Xiaohong Xu, Xiangning Li, Hui Gong, Peng Cao, Qing-Feng Wu","doi":"10.1016/j.neuron.2025.08.021","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.08.021","url":null,"abstract":"Given the evolutionary instinct for caloric intake and frequent weight rebound after diet or drug cessation, increasing energy expenditure emerges as an alternative obesity treatment. Environmental cues such as cold and seasonal light prompt the brain to adjust energy expenditure, yet the coordinating neural mechanisms remain poorly understood. Here, we identify a hypothalamic GABAergic neuronal subtype, marked by Crabp1, that targets multiple nuclei to regulate energy expenditure in mice. Silencing Crabp1 neurons reduces physical activity, body temperature, and adaptive thermogenesis, leading to obesity, whereas activation increases energy expenditure and mitigates diet-induced obesity. Structural and functional analyses reveal that Crabp1 neurons promote energy metabolism through a \"one-to-many\" projection pattern. While Crabp1 neurons are activated by cold exposure and physical activity, prolonged light exposure abrogates their firing, which mediates light-induced metabolic disorder. Together, we reveal a neural basis that integrates various physiological and environmental stimuli to control energy expenditure and body weight.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086613","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

Dynamic redistribution of AMPA receptors toward memory-related neuronal ensembles in mice barrel cortex during sensory learning. 小鼠感觉学习过程中AMPA受体向记忆相关神经元群的动态再分布。

IF 15 1区医学

Neuron Pub Date : 2025-09-17 Epub Date: 2025-07-09 DOI: 10.1016/j.neuron.2025.06.002

Junzhao Li, Rubing Zhou, Jinpeng Wang, Xiaochen Zhang, Yongfeng Li, Chuanyu Edward Li, Bin He, Chenyang Li, Changying Li, Shuai Long, Kongjie Lu, Zhaodi Liu, Rong Zhang, Chen Zhang, Yong Zhang

{"title":"Dynamic redistribution of AMPA receptors toward memory-related neuronal ensembles in mice barrel cortex during sensory learning.","authors":"Junzhao Li, Rubing Zhou, Jinpeng Wang, Xiaochen Zhang, Yongfeng Li, Chuanyu Edward Li, Bin He, Chenyang Li, Changying Li, Shuai Long, Kongjie Lu, Zhaodi Liu, Rong Zhang, Chen Zhang, Yong Zhang","doi":"10.1016/j.neuron.2025.06.002","DOIUrl":"10.1016/j.neuron.2025.06.002","url":null,"abstract":"Understanding the dynamic processes of sensory learning and memory is essential for comprehending cognitive function. How neurons undergo synaptic changes at the receptor level in vivo to form a memory engram remains unclear. Here, we employed a genetic approach and identified memory-related (Robust Activity Marking [RAM+]) neuronal ensembles in the barrel cortex following a sensory detection task. Manipulation of RAM+ neurons replicated licking behavior, demonstrating their role in memory encoding. We observed a layer-selective activation pattern during learning with L2/3 excitatory neurons as primary targets. Two-photon in vivo imaging revealed distinct changes in spine surface GluA1 in L2/3 RAM+ and RAM- neurons during learning; both correlate with learning performance. Furthermore, connections between L4 and L2/3 RAM+ neurons were selectively strengthened during learning. Together, these results reveal a learning-induced α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) redistribution toward active neuronal ensembles in a layer-selective manner, which advances our understanding of cellular and synaptic mechanisms underlying sensory memory formation.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"2979-2996.e8"},"PeriodicalIF":15.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608883","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

Opposing, multiplexed information in lateral and ventral orbitofrontal cortex guides sequential foraging decisions in rats. 相反，在外侧和腹侧眶额皮质的多重信息指导顺序觅食决策的大鼠。

IF 15 1区医学

Neuron Pub Date : 2025-09-17 Epub Date: 2025-07-21 DOI: 10.1016/j.neuron.2025.06.009

Paul J Cunningham, A David Redish

引用次数: 0

Sensory learning induces circuit-level redistribution of AMPARs in the barrel cortex. 感觉学习诱导了桶状皮质中ampar在回路水平上的重新分配。

IF 15 1区医学

Neuron Pub Date : 2025-09-17 DOI: 10.1016/j.neuron.2025.08.001

Xiaonan Li, Simon X Chen

引用次数: 0

Branch logic: Dendritic computations diversify inhibition. 分支逻辑：树突计算多样化抑制。

IF 15 1区医学

Neuron Pub Date : 2025-09-17 DOI: 10.1016/j.neuron.2025.07.023

Sabine Rannio, Shawniya Alageswaran, P Jesper Sjöström

引用次数: 0

Selective loss of Scn2a in ventral tegmental area dopaminergic neurons leads to dopamine system hypofunction and autistic-like behaviors. 腹侧被盖区多巴胺能神经元Scn2a的选择性缺失导致多巴胺系统功能减退和自闭症样行为。

IF 15 1区医学

Neuron Pub Date : 2025-09-17 Epub Date: 2025-07-10 DOI: 10.1016/j.neuron.2025.06.003

Liang Li, Qi Huang, Jiahao Hu, Mengmeng Jin, Yizhou Zhuo, Wei Ke, Quansheng He, Yujie Xiao, Xiaoxue Zhang, Weisheng Wang, Tian-Lin Cheng, Yilin Tai, Feifan Guo, Jintai Yu, Yulong Li, Jie He, Bo Li, Yousheng Shu

{"title":"Selective loss of Scn2a in ventral tegmental area dopaminergic neurons leads to dopamine system hypofunction and autistic-like behaviors.","authors":"Liang Li, Qi Huang, Jiahao Hu, Mengmeng Jin, Yizhou Zhuo, Wei Ke, Quansheng He, Yujie Xiao, Xiaoxue Zhang, Weisheng Wang, Tian-Lin Cheng, Yilin Tai, Feifan Guo, Jintai Yu, Yulong Li, Jie He, Bo Li, Yousheng Shu","doi":"10.1016/j.neuron.2025.06.003","DOIUrl":"10.1016/j.neuron.2025.06.003","url":null,"abstract":"Dopamine hypothesis has been proposed as a mechanism of autism spectrum disorder (ASD), a neurodevelopmental disorder closely associated with genetic mutations. Loss-of-function mutation of SCN2A, which encodes the voltage-gated Na+ channel NaV1.2, is a high risk factor for autism, but whether its pathogenesis is attributable to dopamine system dysfunction remains unclear. Here, we found that Scn2a is the predominant isoform and contributes largely to Na+ currents along the somato-axonal axis of dopaminergic neurons (DANs) in mouse ventral tegmental area (VTA). Complete deletion of Scn2a in VTA DANs reduces their spiking activity and dopamine release, leading to hyperactivity, impaired sociability, and insufficient anxiety. Similar alterations were observed in Scn2a heterozygous mice. Importantly, acute treatment with levodopa alleviates non-motor behavior deficits. Together, the results reveal that Scn2a loss in VTA DANs alone causes autistic-like behaviors through a dopamine-hypofunction mechanism and also provide a possible pharmacotherapy through dopamine replacement for ASD with SCN2A mutations.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"2997-3014.e8"},"PeriodicalIF":15.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619445","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 role of mesolimbic circuitry in aversive signaling and opioid dependence. 中脑边缘回路在厌恶信号传导和阿片依赖中的作用。

IF 15 1区医学

Neuron Pub Date : 2025-09-17 DOI: 10.1016/j.neuron.2025.08.019

Paulo Branco, Julia Cox, Yichen Wu, Sage L Morison, Jones G Parker, Talia N Lerner, Marco Martina, Rajeshwar Awatramani, D James Surmeier, A Vania Apkarian

{"title":"The role of mesolimbic circuitry in aversive signaling and opioid dependence.","authors":"Paulo Branco, Julia Cox, Yichen Wu, Sage L Morison, Jones G Parker, Talia N Lerner, Marco Martina, Rajeshwar Awatramani, D James Surmeier, A Vania Apkarian","doi":"10.1016/j.neuron.2025.08.019","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.08.019","url":null,"abstract":"Positive reinforcement via mu-opioid receptor-mediated disinhibition of ventral tegmental area (VTA) dopamine neurons is crucial in opioid use disorder (OUD). However, VTA dopamine neurons are more heterogeneous than initially thought, both at the molecular and computational levels. Besides encoding reward prediction error, subpopulations of dopamine neurons have also been proposed to encode salience and aversion. How opioid use alters these distinct encoding properties remains unclear. Negative reinforcement-learning to avoid adverse outcomes like withdrawal-also drives chronic drug use, implicating the mesolimbic dopamine system in both positive and negative reinforcement in OUD. This review explores how chronic opioid use modifies heterogeneous VTA neuron populations, enhancing sensitivity to aversive stimuli, promoting negative affect, and motivating withdrawal-avoidance behaviors. We also examine how chronic pain may amplify these effects and discuss the importance of charting circuit-level interactions between chronic pain and OUD for clinical translation.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086616","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 how and why of sleep: Motor theory and catecholamine hypothesis. 睡眠的方式和原因：运动理论和儿茶酚胺假说。

IF 15 1区医学

Neuron Pub Date : 2025-09-16 DOI: 10.1016/j.neuron.2025.08.017

Chenyan Ma, Yang Dan

{"title":"The how and why of sleep: Motor theory and catecholamine hypothesis.","authors":"Chenyan Ma, Yang Dan","doi":"10.1016/j.neuron.2025.08.017","DOIUrl":"10.1016/j.neuron.2025.08.017","url":null,"abstract":"Sleep entails profound changes in the brain and body, marked by altered states of consciousness and reduced somatic and autonomic motor activity. Regarding \"how\" sleep is regulated, whole-brain screening revealed large sleep-control networks spanning the forebrain, midbrain, and hindbrain. We unify diverse experimental evidence under a \"motor theory,\" in which the sleep-control mechanism is integral to somatic and autonomic motor circuits. Regarding the \"why\" question, sleep deprivation impairs cognition, emotion, metabolism, and immunity. We propose catecholamine (dopamine, noradrenaline, and adrenaline) inactivation as the fundamental biological process underlying sleep's numerous benefits. Beyond brain arousal and motor activity, catecholamines regulate metabolism and immunity; their sleep-dependent suppression yields wide-ranging advantages, promoting repair and rejuvenation. Furthermore, catecholaminergic neurons are metabolically vulnerable; their need for rest and recovery may drive homeostatic sleep pressure. Together, the motor theory offers a unifying framework for sleep control, while the catecholamine hypothesis posits a core mechanism mediating sleep's multifaceted benefits.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081304","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

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