Neuron最新文献_第8页

A posture subspace in the primary motor cortex. 初级运动皮层中的姿势亚空间。

IF 15 1区医学

Neuron Pub Date : 2025-08-23 DOI: 10.1016/j.neuron.2025.07.030

Patrick J Marino, Lindsay Bahureksa, Carmen Fernández Fisac, Emily R Oby, Adam L Smoulder, Asma Motiwala, Alan D Degenhart, Erinn M Grigsby, Wilsaan M Joiner, Steven M Chase, Byron M Yu, Aaron P Batista

引用次数: 0

Structural insights into the activation of TMEM175 by small molecule. 小分子激活TMEM175的结构研究。

IF 15 1区医学

Neuron Pub Date : 2025-08-22 DOI: 10.1016/j.neuron.2025.07.029

Xuewu Zhu, Meixuan Ping, Heng Liu, Ting Yu, Zhongwen Jiang, Zhenhua Liu, Chanjing Li, Xinjiao Hou, Qinyu Chu, Shuyao Li, Caiwen Mao, Ting Luo, Chunlan Kang, Feng Wang, Chuanyan Yang, Meiqin Tang, Zhidong Jiang, Zhaobing Gao, Hong Liu, H Eric Xu, Beisha Tang, Xi Cheng, Wanchao Yin, Yu Zhou, Ping Li

{"title":"Structural insights into the activation of TMEM175 by small molecule.","authors":"Xuewu Zhu, Meixuan Ping, Heng Liu, Ting Yu, Zhongwen Jiang, Zhenhua Liu, Chanjing Li, Xinjiao Hou, Qinyu Chu, Shuyao Li, Caiwen Mao, Ting Luo, Chunlan Kang, Feng Wang, Chuanyan Yang, Meiqin Tang, Zhidong Jiang, Zhaobing Gao, Hong Liu, H Eric Xu, Beisha Tang, Xi Cheng, Wanchao Yin, Yu Zhou, Ping Li","doi":"10.1016/j.neuron.2025.07.029","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.07.029","url":null,"abstract":"The upregulation of transmembrane protein 175 (TMEM175) has the potential to improve Parkinson's disease (PD) by aiding in the removal of α-synuclein aggregates. Understanding the structural basis of TMEM175 agonisms is crucial for uncovering its therapeutic potential for PD. Here, we have identified the first cryo-electron microscopy (cryo-EM) structure of human TMEM175 complexes with three agonists: DCY1020, DCY1040, and TUG-891. An open state of TMEM175 is unequivocally captured, laying the groundwork for designing more effective agonists. Further investigations using surface plasmon resonance, systematic mutagenesis, whole-endolysosome patch-clamp techniques, and molecular dynamics simulations consistently revealed that DCY1020/1040 binds at the interface between two subunits, inducing an open conformation further augmented by the synergistic agonist TUG-891. Notably, these agonists facilitate the removal of pathological α-synuclein and restore functions of PD-related TMEM175 variants in neurons. Our findings provide proof of concept that drug discovery targeting TMEM175 can develop agonists capable of effectively reducing pathological α-synuclein levels in PD.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962962","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

Human hippocampal ripples align new experiences with a grid-like schema. 人类的海马体波纹将新的体验与网格状的图式联系起来。

IF 15 1区医学

Neuron Pub Date : 2025-08-22 DOI: 10.1016/j.neuron.2025.07.028

Zhibing Xiao, Xiongfei Wang, Jinbo Zhang, Jianxin Ou, Li He, Yukun Qu, Xiangyu Hu, Timothy E J Behrens, Yunzhe Liu

{"title":"Human hippocampal ripples align new experiences with a grid-like schema.","authors":"Zhibing Xiao, Xiongfei Wang, Jinbo Zhang, Jianxin Ou, Li He, Yukun Qu, Xiangyu Hu, Timothy E J Behrens, Yunzhe Liu","doi":"10.1016/j.neuron.2025.07.028","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.07.028","url":null,"abstract":"Humans form cognitive maps that enable inferences beyond direct experience, relying on hexagonal grid-cell-like neural codes as a schema for two-dimensional (2D) spaces. However, how new experiences align with this schema remains unknown. We recorded intracranial activity from 42 epilepsy patients while they learned rank relations among feature objects, then combined these features into compounds occupying a 2D conceptual space. Hippocampal ripples during brief pauses between learning trials increased with experience, signaling integration of the learned ranks. Crucially, ripple activity during post-learning rest predicted the later appearance of grid-like codes in the entorhinal and medial prefrontal cortex (mPFC) when participants inferred unseen relations among compounds. Ripples synchronized with mPFC during rest were specifically associated with later schema-based inference rather than direct memory retrieval. These findings show that hippocampal ripples align new experiences with an existing grid-like schema, transforming discrete events into structured knowledge that supports flexible reasoning in human cognition.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963033","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

Lipid metabolism alterations in peripheral neuropathies. 周围神经病变的脂质代谢改变。

IF 15 1区医学

Neuron Pub Date : 2025-08-20 Epub Date: 2025-04-30 DOI: 10.1016/j.neuron.2025.04.006

Alessio Silva, Robert Prior, Maurizio D'Antonio, Johannes V Swinnen, Ludo Van Den Bosch

引用次数: 0

In vivo 7 Tesla MRI of non-human primate intracortical microvascular architecture. 非人类灵长类动物皮层内微血管结构的体内特斯拉MRI。

IF 15 1区医学

Neuron Pub Date : 2025-08-20 Epub Date: 2025-07-24 DOI: 10.1016/j.neuron.2025.05.028

Jianbao Wang, Yipeng Liu, Yuhan Ma, Yuqi Feng, Libo Lin, An Ping, Feiyan Tian, Xiaotong Zhang, Avery J L Berman, Saskia Bollmann, Jonathan R Polimeni, Anna Wang Roe

{"title":"In vivo 7 Tesla MRI of non-human primate intracortical microvascular architecture.","authors":"Jianbao Wang, Yipeng Liu, Yuhan Ma, Yuqi Feng, Libo Lin, An Ping, Feiyan Tian, Xiaotong Zhang, Avery J L Berman, Saskia Bollmann, Jonathan R Polimeni, Anna Wang Roe","doi":"10.1016/j.neuron.2025.05.028","DOIUrl":"10.1016/j.neuron.2025.05.028","url":null,"abstract":"Intracortical arterioles are key locations for blood flow regulation and oxygen supply in the brain and are critical to brain health and disease. However, imaging such small (<100-μm-sized) vessels in humans is challenging. Here, using non-human primates as a model, we developed a capability for imaging microvasculature in vivo with a clinical 7 T MRI scanner. Using simulations, we identified parameters for imaging intracortical vessels with slow flow and combined this with high-resolution imaging (64 × 64 μm2 in-plane). Across large swaths of occipital, parietal, and temporal cortex, arrays of intracortical arterioles and venules were observed in gyral crowns and deep within sulcal folds. Systematic arteriole-venule patterns revealed potential architecture of input-output flow relationships. Even single vessels could be followed across cortical laminae. As a first step toward imaging microvasculature in humans, this method introduces a new technology and animal model for understanding relationships between functional and vascular architectures.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"2621-2635.e5"},"PeriodicalIF":15.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718241","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 hypothalamic "glucostat'': CRF neurons decode energy signals. 下丘脑“胰糖素”：CRF神经元解码能量信号。

IF 15 1区医学

Neuron Pub Date : 2025-08-20 DOI: 10.1016/j.neuron.2025.07.021

Ibukun Akinrinade, Jaideep S Bains

引用次数: 0

Is criticality a unified setpoint of brain function? 临界状态是大脑功能的统一设定值吗？

IF 15 1区医学

Neuron Pub Date : 2025-08-20 Epub Date: 2025-06-23 DOI: 10.1016/j.neuron.2025.05.020

Keith B Hengen, Woodrow L Shew

引用次数: 0

The cell-surface shared proteome of astrocytes and neurons and the molecular foundations of their multicellular interactions. 星形胶质细胞和神经元的细胞表面共享蛋白质组及其多细胞相互作用的分子基础。

IF 15 1区医学

Neuron Pub Date : 2025-08-20 Epub Date: 2025-06-10 DOI: 10.1016/j.neuron.2025.05.019

Ling Wu, Vijaya Pandey, Vanessa H Casha, Zhe Qu, Yasaman Jami-Alahmadi, Viviana Gradinaru, James A Wohlschlegel, Baljit S Khakh

{"title":"The cell-surface shared proteome of astrocytes and neurons and the molecular foundations of their multicellular interactions.","authors":"Ling Wu, Vijaya Pandey, Vanessa H Casha, Zhe Qu, Yasaman Jami-Alahmadi, Viviana Gradinaru, James A Wohlschlegel, Baljit S Khakh","doi":"10.1016/j.neuron.2025.05.019","DOIUrl":"10.1016/j.neuron.2025.05.019","url":null,"abstract":"Neurons and astrocytes are predominant brain cells that extensively interact, but the molecular basis of their interactions remains largely unexplored. We identified and mapped striatal astrocytic and neuronal cell-surface proteins (CSPs) and found that many were shared, representing the cell-surface shared proteome of astrocytes and neurons (CS SPAN) bridging striatal astrocyte-neuron interaction sites. CS SPAN was replete with extracellular matrix proteins, cell adhesion molecules, transporters, ion channels, and G protein-coupled receptors. By mapping the cellular origins of astrocytic CSPs, we identified astrocytic interactions with diverse parenchymal cells. Broadly concordant with human data, in a mouse model of Huntington's disease (HD), pathophysiology and its genetic attenuation were accompanied by altered and restored CS SPAN and CSPs, respectively. CS SPAN also included molecules dysregulated in diverse brain disorders. Our study reveals the astrocyte-neuron interface in molecular terms and provides a mechanistic foundation for exploring its physiological roles and contributions to brain diseases.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"2599-2620.e7"},"PeriodicalIF":15.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275480","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

Voltage imaging reveals circuit computations in the raphe underlying serotonin-mediated motor vigor learning. 电压成像揭示了神经中脑的电路计算，其基础是血清素介导的运动活力学习。

IF 15 1区医学

Neuron Pub Date : 2025-08-20 Epub Date: 2025-06-10 DOI: 10.1016/j.neuron.2025.05.017

Takashi Kawashima, Ziqiang Wei, Ravid Haruvi, Inbal Shainer, Sujatha Narayan, Herwig Baier, Misha B Ahrens

{"title":"Voltage imaging reveals circuit computations in the raphe underlying serotonin-mediated motor vigor learning.","authors":"Takashi Kawashima, Ziqiang Wei, Ravid Haruvi, Inbal Shainer, Sujatha Narayan, Herwig Baier, Misha B Ahrens","doi":"10.1016/j.neuron.2025.05.017","DOIUrl":"10.1016/j.neuron.2025.05.017","url":null,"abstract":"As animals adapt to new situations, neuromodulation is a potent way to alter behavior, yet mechanisms by which neuromodulatory nuclei compute during behavior are underexplored. The serotonergic raphe supports motor learning in larval zebrafish by visually detecting distance traveled during swims, encoding action effectiveness, and modulating motor vigor. We tracked the raphe's input-output computations at millisecond timescales using voltage and neurotransmitter imaging and found that swimming opens a gate for visual input to cause spiking in serotonergic neurons, enabling the encoding of action outcomes and filtering out learning-irrelevant visual signals. Specifically, swim commands initially inhibited serotonergic neurons via γ-aminobutyric acid (GABA). Immediately after, membrane voltage increased via post-inhibitory rebound, allowing swim-induced visual motion to evoke firing through glutamate, triggering serotonin release to modulate future motor vigor. Ablating local GABAergic neurons impaired raphe coding and motor learning. Thus, serotonergic neuromodulation arises from action-outcome coincidence detection within the raphe.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"2692-2707.e8"},"PeriodicalIF":15.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275481","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

Adaptive reinforcement learning is causally supported by anterior cingulate cortex and striatum. 适应性强化学习是由前扣带皮层和纹状体支持的。

IF 15 1区医学

Neuron Pub Date : 2025-08-20 Epub Date: 2025-06-10 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":"2708-2723.e7"},"PeriodicalIF":15.0,"publicationDate":"2025-08-20","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