Neuron最新文献 - Book学术

Strategies for mitigating data heterogeneities in AI-based neuro-disease detection.

IF 14.7 1区医学

Neuron Pub Date : 2025-02-25 DOI: 10.1016/j.neuron.2025.01.028

Matthew Leming, Kyungsu Kim, Rose Bruffaerts, Hyungsoon Im

引用次数: 0

BACE1-dependent cleavage of GABA_A receptor contributes to neural hyperexcitability and disease progression in Alzheimer's disease.

IF 14.7 1区医学

Neuron Pub Date : 2025-02-25 DOI: 10.1016/j.neuron.2025.01.030

Danlei Bi, Hong Bao, Xiaoli Yang, Zujun Wu, Xiaoxu Yang, Guangwei Xu, Xiaoming Liu, Zhikun Wan, Jiachen Liu, Junju He, Lang Wen, Yuying Jing, Ruijie Zhu, Zhenyu Long, Yating Rong, Dongxu Wang, Xiaoqun Wang, Wei Xiong, Guangming Huang, Feng Gao, Yong Shen

{"title":"BACE1-dependent cleavage of GABAA receptor contributes to neural hyperexcitability and disease progression in Alzheimer's disease.","authors":"Danlei Bi, Hong Bao, Xiaoli Yang, Zujun Wu, Xiaoxu Yang, Guangwei Xu, Xiaoming Liu, Zhikun Wan, Jiachen Liu, Junju He, Lang Wen, Yuying Jing, Ruijie Zhu, Zhenyu Long, Yating Rong, Dongxu Wang, Xiaoqun Wang, Wei Xiong, Guangming Huang, Feng Gao, Yong Shen","doi":"10.1016/j.neuron.2025.01.030","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.01.030","url":null,"abstract":"Neural hyperexcitability has been clinically associated with amyloid-β (Aβ) pathology and cognitive impairment in Alzheimer's disease (AD). Here, we show that decreased GABAA receptor (GABAAR) currents are linked to hippocampal granule cell hyperexcitability in the AD mouse model APP23. Elevated levels of β-secretase (BACE1), the β-secretase responsible for generating Aβ peptides, lead to aberrant cleavage of GABAAR β1/2/3 subunits in the brains of APP23 mice and AD patients. Moreover, BACE1-dependent cleavage of the β subunits leads to a decrease in GABAAR-mediated inhibitory currents in BACE1 transgenic mice. Finally, we show that the neural hyperexcitability, Aβ load, and spatial memory deficit phenotypes of APP23 mice are significantly reduced upon the granule cell expression of a non-cleavable β3 subunit mutant. Collectively, our study establishes that BACE1-dependent cleavage of GABAAR β subunits promotes the pathological hyperexcitability known to drive neurodegeneration and cognitive impairment in the AD brain, suggesting that prevention of the cleavage could slow disease progression.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523900","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

Dietary availability acutely influences puberty onset via a hypothalamic neural circuit.

IF 14.7 1区医学

Neuron Pub Date : 2025-02-24 DOI: 10.1016/j.neuron.2025.01.015

Teppei Goto, Mitsue Hagihara, Satsuki Irie, Takaya Abe, Hiroshi Kiyonari, Kazunari Miyamichi

引用次数: 0

Differential modification of ascending spinal outputs in acute and chronic pain states.

IF 14.7 1区医学

Neuron Pub Date : 2025-02-21 DOI: 10.1016/j.neuron.2025.01.031

David A Yarmolinsky, Xiangsunze Zeng, Natalie MacKinnon-Booth, Caitlin A Greene, Chloe Kim, Yu-Ting Cheng, Bruna Lenfers Turnes, Clifford J Woolf

{"title":"Differential modification of ascending spinal outputs in acute and chronic pain states.","authors":"David A Yarmolinsky, Xiangsunze Zeng, Natalie MacKinnon-Booth, Caitlin A Greene, Chloe Kim, Yu-Ting Cheng, Bruna Lenfers Turnes, Clifford J Woolf","doi":"10.1016/j.neuron.2025.01.031","DOIUrl":"10.1016/j.neuron.2025.01.031","url":null,"abstract":"Pain hypersensitivity arises from the induction of plasticity in peripheral and spinal somatosensory neurons, which modifies nociceptive input to the brain, altering pain perception. We applied longitudinal calcium imaging of spinal dorsal projection neurons to determine whether and how the representation of somatosensory stimuli in the anterolateral tract, the principal pathway transmitting nociceptive signals to the brain, changes between distinct pain states. In healthy mice, we identified stable outputs selective for cooling or warming and a neuronal ensemble activated by noxious thermal and mechanical stimuli. Induction of acute peripheral sensitization by topical capsaicin transiently re-tuned nociceptive output neurons to encode low-intensity stimuli. In contrast, peripheral nerve injury resulted in a persistent suppression of innocuous spinal outputs coupled with persistent activation of a normally silent population of high-threshold neurons. These results demonstrate differential modulation of spinal outputs to the brain during nociceptive and neuropathic pain states.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537487","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

Universal statistics of hippocampal place fields across species and dimensionalities.

IF 14.7 1区医学

Neuron Pub Date : 2025-02-20 DOI: 10.1016/j.neuron.2025.01.017

Nischal Mainali, Rava Azeredo da Silveira, Yoram Burak

引用次数: 0

Retraction Notice to: Conditional Deletion of All Neurexins Defines Diversity of Essential Synaptic Organizer Functions for Neurexins.

IF 14.7 1区医学

Neuron Pub Date : 2025-02-19 Epub Date: 2025-02-11 DOI: 10.1016/j.neuron.2025.01.027

Lulu Y Chen, Man Jiang, Bo Zhang, Ozgun Gokce, Thomas C Südhof

引用次数: 0

Dennis D.M. O'Leary (1954-2024). 丹尼斯-奥利里（Dennis D.M.O'Leary，1954-2024 年）。

IF 14.7 1区医学

Neuron Pub Date : 2025-02-19 DOI: 10.1016/j.neuron.2025.01.020

Shen-Ju Chou, Robert Hindges, Todd McLaughlin, Yasushi Nakagawa, Linda J Richards, Adina L Roskies, Setsuko Sahara, Bradley L Schlaggar, Kathleen T Yee

引用次数: 0

An extensive dataset of spiking activity to reveal the syntax of the ventral stream. 一个广泛的尖峰活动数据集，揭示腹侧流的语法。

IF 14.7 1区医学

Neuron Pub Date : 2025-02-19 Epub Date: 2025-01-13 DOI: 10.1016/j.neuron.2024.12.003

Paolo Papale, Feng Wang, Matthew W Self, Pieter R Roelfsema

引用次数: 0

An intermediate open structure reveals the gating transition of the mechanically activated PIEZO1 channel. 中间开放结构揭示了机械激活的PIEZO1通道的门控转变。

IF 14.7 1区医学

Neuron Pub Date : 2025-02-19 Epub Date: 2024-12-23 DOI: 10.1016/j.neuron.2024.11.020

Sijia Liu, Xuzhong Yang, Xudong Chen, Xiaochun Zhang, Jinghui Jiang, Jingyi Yuan, Wenhao Liu, Li Wang, Heng Zhou, Kun Wu, Boxue Tian, Xueming Li, Bailong Xiao

{"title":"An intermediate open structure reveals the gating transition of the mechanically activated PIEZO1 channel.","authors":"Sijia Liu, Xuzhong Yang, Xudong Chen, Xiaochun Zhang, Jinghui Jiang, Jingyi Yuan, Wenhao Liu, Li Wang, Heng Zhou, Kun Wu, Boxue Tian, Xueming Li, Bailong Xiao","doi":"10.1016/j.neuron.2024.11.020","DOIUrl":"10.1016/j.neuron.2024.11.020","url":null,"abstract":"PIEZO1 is a mechanically activated cation channel that undergoes force-induced activation and inactivation. However, its distinct structural states remain undefined. Here, we employed an open-prone PIEZO1-S2472E mutant to capture an intermediate open structure. Compared with the curved and flattened structures of PIEZO1, the S2472E-Intermediate structure displays partially flattened blades, a downward and rotational motion of the top cap, and a spring-like compression of the linker connecting the cap to the pore-lining inner helix. These conformational changes open the cap gate and the hydrophobic transmembrane gate, whereas the intracellular lateral plug gate remains closed. The flattened structure of PIEZO1 with an up-state cap and closed cap gate might represent an inactivated state. Molecular dynamics (MD) simulations of ion conduction support the closed, intermediate open, and inactivated structural states. Mutagenesis and electrophysiological studies identified key domains and residues critical for the mechanical activation of PIEZO1. These studies collectively define the distinct structural states and gating transitions of PIEZO1.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"590-604.e6"},"PeriodicalIF":14.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886097","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

Tachykinin signaling in the right parabrachial nucleus mediates early-phase neuropathic pain development. 右臂旁核的速激肽信号介导早期神经性疼痛的发展。

IF 14.7 1区医学

Neuron Pub Date : 2025-02-19 Epub Date: 2024-12-23 DOI: 10.1016/j.neuron.2024.11.021

Yinxia Li, Ngoc T Ha, Juan Li, Yaxin Yan, Qian Chen, Liping Cai, Weike Li, Shoupei Liu, Bo Li, Tianlin Cheng, Yangang Sun, Yingwei Wang, Juan Deng

{"title":"Tachykinin signaling in the right parabrachial nucleus mediates early-phase neuropathic pain development.","authors":"Yinxia Li, Ngoc T Ha, Juan Li, Yaxin Yan, Qian Chen, Liping Cai, Weike Li, Shoupei Liu, Bo Li, Tianlin Cheng, Yangang Sun, Yingwei Wang, Juan Deng","doi":"10.1016/j.neuron.2024.11.021","DOIUrl":"10.1016/j.neuron.2024.11.021","url":null,"abstract":"The lateral parabrachial nucleus (PBN) is critically involved in neuropathic pain modulation. However, the cellular and molecular mechanisms underlying this process remain largely unknown. Here, we report that in mice, the right-sided, but not the left-sided, PBN plays an essential role in the development of hyperalgesia following nerve injury, irrespective of the injury side. Spino-parabrachial pathways targeting the right-sided PBN display short-term facilitation, and right-sided PBN neurons exhibit an increase in the excitability and activity after nerve injury. Inhibiting Tacr1-positive neurons, blocking Tacr1-encoding tachykinin 1 receptor (NK1R), or knocking down the Tacr1 gene in the right-sided, rather than left-sided, PBN alleviates neuropathic pain-induced sensory hypersensitivity. Additionally, the right-sided PBN plays a critical role in the development of hyperalgesia during the early phase of neuropathic pain. These results highlight the essential role of NK1R in the lateralized modulation of neuropathic pain by the PBN, providing new insights into the mechanisms underlying neuropathic pain.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"605-619.e6"},"PeriodicalIF":14.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886098","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