IF 14.7 1区医学

Neuron Pub Date : 2025-06-05 DOI: 10.1016/j.neuron.2025.05.018

Robert Louis Treuting, Kianoush Banaie Boroujeni, Charles Grimes Gerrity, Adam Neumann, Paul Tiesinga, Thilo Womelsdorf

{"title":"Adaptive reinforcement learning is causally supported by anterior cingulate cortex and striatum.","authors":"Robert Louis Treuting, Kianoush Banaie Boroujeni, Charles Grimes Gerrity, Adam Neumann, Paul Tiesinga, Thilo Womelsdorf","doi":"10.1016/j.neuron.2025.05.018","DOIUrl":"10.1016/j.neuron.2025.05.018","url":null,"abstract":"Reinforcement learning can benefit from adaptive strategies that adjust exploration-exploitation levels, leverage working memory, or guide attention toward relevant information. We tested how the anterior cingulate cortex (ACC) and the striatum support these processes during learning of feature-based attention at varying feature uncertainty and motivational saliency. Brief, gaze-contingent electrical stimulation affected adaptive reinforcement learning in ACC and the striatum at high feature uncertainty, but in opposite ways. ACC stimulation impaired learning, while striatum stimulation improved learning. Modeling showed that ACC stimulation impaired optimizing exploration and use of prediction errors to reduce uncertainty, while striatum stimulation improved the updating of value expectations. These findings were consistent with neuronal selectivity. In ACC, neurons tracked error history and fired more strongly during more uncertain choices, while in the striatum, neurons fired more strongly during more certain, higher-value choices. These results show that the ACC and the striatum optimize the guidance of exploration toward reward-relevant objects during periods of uncertainty.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275479","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

Fibril fuzzy coat is important for α-synuclein pathological transmission activity. 纤维绒毛被对α-突触核蛋白的病理传递活性起重要作用。

IF 14.7 1区医学

Neuron Pub Date : 2025-06-04 Epub Date: 2025-04-10 DOI: 10.1016/j.neuron.2025.03.019

Yuliang Han, Juan Li, Wencheng Xia, Qintong Li, Zihan Sun, Wen Zeng, Yingxin Hu, Kelvin C Luk, Cong Liu, ShengQi Xiang, Zhuohao He

{"title":"Fibril fuzzy coat is important for α-synuclein pathological transmission activity.","authors":"Yuliang Han, Juan Li, Wencheng Xia, Qintong Li, Zihan Sun, Wen Zeng, Yingxin Hu, Kelvin C Luk, Cong Liu, ShengQi Xiang, Zhuohao He","doi":"10.1016/j.neuron.2025.03.019","DOIUrl":"10.1016/j.neuron.2025.03.019","url":null,"abstract":"α-synuclein transmission and propagation are hallmarks of synucleinopathies, yet the molecular mechanisms remain elusive. Using α-synuclein preformed fibrils as pathological seeds, we observed a gradual decline in neuronal transmission activity during serial propagation. Fibril polymorphisms were identified from the initial generation: mini-P, with higher neuronal seeding activity, and mini-S, which accelerated recombinant α-synuclein aggregation. Changes in their proportions during propagation explained the overall decline in transmission activity. Cryoelectron microscopy and solid-state nuclear magnetic resonance revealed that both fibrils shared similar core regions but differed in their fuzzy coat flexibilities. The interaction between the fuzzy coat and fibril core substantially influenced neuronal transmission, a model further supported by hydrogen/deuterium exchange mass spectrometry. A mini-P-selective antibody identified active fibril types in newly propagated brain regions in human synucleinopathies. This study highlights the fuzzy coat's pivotal role in pathological protein transmission and suggests it as a potential therapeutic target for synucleinopathies.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"1723-1740.e7"},"PeriodicalIF":14.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022968","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

Combining old with new: A novel approach to studying human brain metabolism. 新旧结合：一种研究人脑代谢的新方法。

IF 14.7 1区医学

Neuron Pub Date : 2025-06-04 DOI: 10.1016/j.neuron.2025.04.031

Tyler Blazey, Manu S Goyal

引用次数: 0

Comprehensive characterization of metabolic consumption and production by the human brain. 人脑代谢消耗和产生的综合表征。

IF 14.7 1区医学

Neuron Pub Date : 2025-06-04 Epub Date: 2025-03-26 DOI: 10.1016/j.neuron.2025.03.003

Yilong Wang, Lebo Zhou, Nan Wang, Baoshan Qiu, Di Yao, Jie Yu, Miaoqing He, Tong Li, Yufeng Xie, Xiaoqian Yu, Zhanying Bi, Xiangli Sun, Xunming Ji, Zhen Li, Dapeng Mo, Woo-Ping Ge

{"title":"Comprehensive characterization of metabolic consumption and production by the human brain.","authors":"Yilong Wang, Lebo Zhou, Nan Wang, Baoshan Qiu, Di Yao, Jie Yu, Miaoqing He, Tong Li, Yufeng Xie, Xiaoqian Yu, Zhanying Bi, Xiangli Sun, Xunming Ji, Zhen Li, Dapeng Mo, Woo-Ping Ge","doi":"10.1016/j.neuron.2025.03.003","DOIUrl":"10.1016/j.neuron.2025.03.003","url":null,"abstract":"Metabolism is vital for brain function. However, a systematic investigation to understand the metabolic exchange between the human brain and circulatory system has been lacking. Here, we compared metabolomes and lipidomes of blood samples from the cerebral venous sinus and femoral artery to profile the brain's uptake and release of metabolites and lipids (1,365 metabolites and 140 lipids). We observed a high net uptake of glucose, taurine, and hypoxanthine and identified glutamine and pyruvate as significantly released metabolites by the brain. Triacylglycerols are the most prominent class of lipid consumed by the brain. The brain with cerebral venous sinus stenosis (CVSS) consumed more glucose and lactate and released more glucose metabolism byproducts than the brain with cerebral venous sinus thrombosis (CVST). Our data also showed age-related alterations in the uptake and release of metabolites. These results provide a comprehensive view of metabolic consumption and production processes within the human brain.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"1708-1722.e5"},"PeriodicalIF":14.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730945","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

A microglia identity crisis. 小胶质细胞身份危机。

IF 14.7 1区医学

Neuron Pub Date : 2025-06-04 DOI: 10.1016/j.neuron.2025.05.008

Jessie Axsom, F Chris Bennett

引用次数: 0

Dynorphin modulates reward-seeking actions through a pallido-amygdala cholinergic circuit. Dynorphin通过苍白体-杏仁核胆碱能回路调节寻求奖励的行为。

IF 14.7 1区医学

Neuron Pub Date : 2025-06-04 Epub Date: 2025-04-15 DOI: 10.1016/j.neuron.2025.03.018

Qingtao Sun, Mingzhe Liu, Wuqiang Guan, Xiong Xiao, Chunyang Dong, Michael R Bruchas, Larry S Zweifel, Yulong Li, Lin Tian, Bo Li

{"title":"Dynorphin modulates reward-seeking actions through a pallido-amygdala cholinergic circuit.","authors":"Qingtao Sun, Mingzhe Liu, Wuqiang Guan, Xiong Xiao, Chunyang Dong, Michael R Bruchas, Larry S Zweifel, Yulong Li, Lin Tian, Bo Li","doi":"10.1016/j.neuron.2025.03.018","DOIUrl":"10.1016/j.neuron.2025.03.018","url":null,"abstract":"The endogenous opioid peptide dynorphin and its receptor κ-opioid receptor (KOR) have been implicated in divergent behaviors, but the underlying mechanisms remain elusive. Here, we show that dynorphin released from nucleus accumbens dynorphinergic neurons exerts powerful modulation over a ventral pallidum (VP) disinhibitory circuit, thereby controlling cholinergic transmission to the amygdala and reward-seeking behavior in mice. On one hand, dynorphin acts postsynaptically via KORs on VP GABAergic neurons to promote disinhibition of cholinergic neurons, which release acetylcholine into the amygdala to facilitate learning and invigorate actions. On the other hand, dynorphin also acts presynaptically via KORs on dynorphinergic terminals to limit its own release. Such autoinhibition keeps cholinergic neurons from prolonged activation and release of acetylcholine and prevents perseverant reward seeking. Our study reveals how dynorphin exquisitely modulates behavior through the cholinergic system and provides an explanation for why these neuromodulators are involved in motivational disorders, including depression and addiction.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"1823-1840.e8"},"PeriodicalIF":14.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974930","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

Activity-dependent development of the body's touch receptors. 身体触觉感受器的活动依赖性发展。

IF 14.7 1区医学

Neuron Pub Date : 2025-06-04 Epub Date: 2025-05-16 DOI: 10.1016/j.neuron.2025.04.015

Celine Santiago, Julianna Siegrist, Nusrat Africawala, Annie Handler, Aniqa Tasnim, Rabia Anjum, Josef Turecek, Brendan P Lehnert, Sophia Renauld, Jinheon Choi, Michael Nolan-Tamariz, Michael Iskols, Alexandra R Magee, Suzanne Paradis, Nikhil Sharma, David D Ginty

{"title":"Activity-dependent development of the body's touch receptors.","authors":"Celine Santiago, Julianna Siegrist, Nusrat Africawala, Annie Handler, Aniqa Tasnim, Rabia Anjum, Josef Turecek, Brendan P Lehnert, Sophia Renauld, Jinheon Choi, Michael Nolan-Tamariz, Michael Iskols, Alexandra R Magee, Suzanne Paradis, Nikhil Sharma, David D Ginty","doi":"10.1016/j.neuron.2025.04.015","DOIUrl":"10.1016/j.neuron.2025.04.015","url":null,"abstract":"We report a role for activity in the development of the primary sensory neurons that detect touch. Genetic deletion of Piezo2, the principal mechanosensitive ion channel in somatosensory neurons, caused profound changes in the formation of mechanosensory end-organ structures. Peripheral-nervous-system-specific deletion of the voltage-gated sodium channel Nav1.6 (Scn8a), which resulted in altered electrophysiological responses to mechanical stimuli, also disrupted somatosensory neuron morphologies, supporting a role for neuronal activity in end-organ formation. Single-cell RNA sequencing of Piezo2 mutants revealed changes in gene expression in sensory neurons activated by light mechanical forces, whereas other neuronal classes were minimally affected, and genetic deletion of Piezo2-dependent genes partially reproduced the defects in mechanosensory neuron structures observed in Piezo2 mutants. These findings indicate that mechanically evoked neuronal activity acts early in life to shape the maturation of mechanosensory end-organs that underlie our sense of gentle touch.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"1758-1773.e9"},"PeriodicalIF":14.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094428","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

A pontine center in descending pain control. 下行疼痛控制中的脑桥中枢。

IF 14.7 1区医学

Neuron Pub Date : 2025-06-04 Epub Date: 2025-03-24 DOI: 10.1016/j.neuron.2025.02.028

Tianming Li, Wenjie Zhou, Jin Ke, Matthew Chen, Zhen Wang, Lauren Hayashi, Xiaojing Su, Wenbin Jia, Wenxi Huang, Chien-Sheng Wang, Kapsa Bengyella, Yang Yang, Rafael Hernandez, Yan Zhang, Xinglei Song, Tianle Xu, Tianwen Huang, Yuanyuan Liu

{"title":"A pontine center in descending pain control.","authors":"Tianming Li, Wenjie Zhou, Jin Ke, Matthew Chen, Zhen Wang, Lauren Hayashi, Xiaojing Su, Wenbin Jia, Wenxi Huang, Chien-Sheng Wang, Kapsa Bengyella, Yang Yang, Rafael Hernandez, Yan Zhang, Xinglei Song, Tianle Xu, Tianwen Huang, Yuanyuan Liu","doi":"10.1016/j.neuron.2025.02.028","DOIUrl":"10.1016/j.neuron.2025.02.028","url":null,"abstract":"Pain sensation changes according to expectation, context, and mood, illustrating how top-down circuits affect somatosensory processing. Here, we used an intersectional strategy to identify anatomical and molecular-spatial features of supraspinal descending neurons activated by distinct noxious stimulation. This approach captured known descending pain pathways as well as spinal projecting neurons that are anatomically mapped to Barrington's nucleus in the dorsal pontine tegmentum. We determined that this population of neurons expresses corticotropin-releasing hormone in Barrington's nucleus (BarCrh) and exhibits time-locked firing in response to noxious stimulation. Chemogenetic activation of BarCrh neurons attenuated nocifensive responses as well as tactile neuropathic pain, while silencing these neurons resulted in thermal hyperalgesia and mechanical allodynia. Mechanistically, we demonstrated that pain-related input from the ventrolateral periaqueductal gray recruits BarCrh neurons, reduces ascending nociceptive transmission, and preferentially activates spinal dynorphin neurons to mediate analgesia. Our data expose a pontine inhibitory descending pathway that powerfully controls nocifensive sensory input to the brain.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"1789-1804.e7"},"PeriodicalIF":14.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710900","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

Pontospinal control of nociception via a negative feedback loop. 通过负反馈回路的桥脊控制伤害感觉。

IF 14.7 1区医学

Neuron Pub Date : 2025-06-04 DOI: 10.1016/j.neuron.2025.05.007

Andrew D Vigotsky, Adrien Tassou, Grégory Scherrer

引用次数: 0

Stem cell sidekicks: ILC2s boost brain healing with a dash of Areg. 干细胞的伙伴：ILC2s通过少量Areg促进大脑愈合。

IF 14.7 1区医学

Neuron Pub Date : 2025-06-04 DOI: 10.1016/j.neuron.2025.04.011

S Thomas Carmichael

引用次数: 0

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