IF 14.7 1区医学

Neuron Pub Date : 2025-02-19 Epub Date: 2025-01-13 DOI: 10.1016/j.neuron.2024.12.009

Anita Lüthi, Maiken Nedergaard

引用次数: 0

A neurodegenerative cellular stress response linked to dark microglia and toxic lipid secretion. 神经退行性细胞应激反应与暗小胶质细胞和毒性脂质分泌有关。

IF 14.7 1区医学

Neuron Pub Date : 2025-02-19 Epub Date: 2024-12-23 DOI: 10.1016/j.neuron.2024.11.018

Anna Flury, Leen Aljayousi, Hye-Jin Park, Mohammadparsa Khakpour, Jack Mechler, Siaresh Aziz, Jackson D McGrath, Pragney Deme, Colby Sandberg, Fernando González Ibáñez, Olivia Braniff, Thi Ngo, Simira Smith, Matthew Velez, Denice Moran Ramirez, Dvir Avnon-Klein, John W Murray, Jia Liu, Martin Parent, Susana Mingote, Norman J Haughey, Sebastian Werneburg, Marie-Ève Tremblay, Pinar Ayata

{"title":"A neurodegenerative cellular stress response linked to dark microglia and toxic lipid secretion.","authors":"Anna Flury, Leen Aljayousi, Hye-Jin Park, Mohammadparsa Khakpour, Jack Mechler, Siaresh Aziz, Jackson D McGrath, Pragney Deme, Colby Sandberg, Fernando González Ibáñez, Olivia Braniff, Thi Ngo, Simira Smith, Matthew Velez, Denice Moran Ramirez, Dvir Avnon-Klein, John W Murray, Jia Liu, Martin Parent, Susana Mingote, Norman J Haughey, Sebastian Werneburg, Marie-Ève Tremblay, Pinar Ayata","doi":"10.1016/j.neuron.2024.11.018","DOIUrl":"10.1016/j.neuron.2024.11.018","url":null,"abstract":"The brain's primary immune cells, microglia, are a leading causal cell type in Alzheimer's disease (AD). Yet, the mechanisms by which microglia can drive neurodegeneration remain unresolved. Here, we discover that a conserved stress signaling pathway, the integrated stress response (ISR), characterizes a microglia subset with neurodegenerative outcomes. Autonomous activation of ISR in microglia is sufficient to induce early features of the ultrastructurally distinct \"dark microglia\" linked to pathological synapse loss. In AD models, microglial ISR activation exacerbates neurodegenerative pathologies and synapse loss while its inhibition ameliorates them. Mechanistically, we present evidence that ISR activation promotes the secretion of toxic lipids by microglia, impairing neuron homeostasis and survival in vitro. Accordingly, pharmacological inhibition of ISR or lipid synthesis mitigates synapse loss in AD models. Our results demonstrate that microglial ISR activation represents a neurodegenerative phenotype, which may be sustained, at least in part, by the secretion of toxic lipids.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"554-571.e14"},"PeriodicalIF":14.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886096","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

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.2025.01.026

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

引用次数: 0

A brain-wide map of descending inputs onto spinal V1 interneurons. 下行输入到脊髓V1中间神经元的全脑图。

IF 14.7 1区医学

Neuron Pub Date : 2025-02-19 Epub Date: 2024-12-23 DOI: 10.1016/j.neuron.2024.11.019

Phillip D Chapman, Anand S Kulkarni, Alexandra J Trevisan, Katie Han, Jennifer M Hinton, Paulina Deltuvaite, Lief E Fenno, Charu Ramakrishnan, Mary H Patton, Lindsay A Schwarz, Stanislav S Zakharenko, Karl Deisseroth, Jay B Bikoff

{"title":"A brain-wide map of descending inputs onto spinal V1 interneurons.","authors":"Phillip D Chapman, Anand S Kulkarni, Alexandra J Trevisan, Katie Han, Jennifer M Hinton, Paulina Deltuvaite, Lief E Fenno, Charu Ramakrishnan, Mary H Patton, Lindsay A Schwarz, Stanislav S Zakharenko, Karl Deisseroth, Jay B Bikoff","doi":"10.1016/j.neuron.2024.11.019","DOIUrl":"10.1016/j.neuron.2024.11.019","url":null,"abstract":"Motor output results from the coordinated activity of neural circuits distributed across multiple brain regions that convey information to the spinal cord via descending motor pathways. Yet the organizational logic through which supraspinal systems target discrete components of spinal motor circuits remains unclear. Here, using viral transsynaptic tracing along with serial two-photon tomography, we have generated a whole-brain map of monosynaptic inputs to spinal V1 interneurons, a major inhibitory population involved in motor control. We identified 26 distinct brain structures that directly innervate V1 interneurons, spanning medullary and pontine regions in the hindbrain as well as cortical, midbrain, cerebellar, and neuromodulatory systems. Moreover, we identified broad but biased input from supraspinal systems onto V1Foxp2 and V1Pou6f2 neuronal subsets. Collectively, these studies reveal elements of biased connectivity and convergence in descending inputs to molecularly distinct interneuron subsets and provide an anatomical foundation for understanding how supraspinal systems influence spinal motor circuits.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"524-538.e6"},"PeriodicalIF":14.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886095","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

Deficiency of histamine H₂ receptors in parvalbumin-positive neurons leads to hyperactivity, impulsivity, and impaired attention. 小蛋白阳性神经元中缺乏组胺H2受体可导致多动、冲动和注意力受损。

IF 14.7 1区医学

Neuron Pub Date : 2025-02-19 Epub Date: 2025-01-08 DOI: 10.1016/j.neuron.2024.12.002

Dadao An, Yi You, Qianyi Ma, Zhengyi Xu, Zonghan Liu, Ruichu Liao, Han Chen, Yiquan Wang, Yi Wang, Haibin Dai, Haohong Li, Lei Jiang, Zhong Chen, Weiwei Hu

{"title":"Deficiency of histamine H2 receptors in parvalbumin-positive neurons leads to hyperactivity, impulsivity, and impaired attention.","authors":"Dadao An, Yi You, Qianyi Ma, Zhengyi Xu, Zonghan Liu, Ruichu Liao, Han Chen, Yiquan Wang, Yi Wang, Haibin Dai, Haohong Li, Lei Jiang, Zhong Chen, Weiwei Hu","doi":"10.1016/j.neuron.2024.12.002","DOIUrl":"10.1016/j.neuron.2024.12.002","url":null,"abstract":"Attention deficit hyperactivity disorder (ADHD), affecting 4% of the population, is characterized by inattention, hyperactivity, and impulsivity; however, its neurophysiological mechanisms remain unclear. Here, we discovered that deficiency of histamine H2 receptor (H2R) in parvalbumin-positive neurons in substantia nigra pars recticulata (PVSNr) attenuates PV+ neuronal activity and induces hyperactivity, impulsivity, and inattention in mice. Moreover, decreased H2R expression was observed in PVSNr in patients with ADHD symptoms and dopamine-transporter-deficient mice, whose behavioral phenotypes were alleviated by H2R agonist treatment. Dysfunction of PVSNr efferents to the substantia nigra pars compacta dopaminergic neurons and superior colliculus differently contributes to H2R-deficiency-induced behavioral disorders. Collectively, our results demonstrate that H2R deficiency in PV+ neurons contributes to hyperactivity, impulsivity, and inattention by dampening PVSNr activity and involving different efferents in mice. It may enhance understanding of the molecular and circuit-level basis of ADHD and afford new potential therapeutic targets for ADHD-like psychiatric diseases.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"572-589.e6"},"PeriodicalIF":14.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952362","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

GPR37L1 identifies spinal cord astrocytes and protects neuropathic pain after nerve injury.

IF 14.7 1区医学

Neuron Pub Date : 2025-02-11 DOI: 10.1016/j.neuron.2025.01.012

Jing Xu, Zihan Yan, Sangsu Bang, Dmitry Velmeshev, Ru-Rong Ji

{"title":"GPR37L1 identifies spinal cord astrocytes and protects neuropathic pain after nerve injury.","authors":"Jing Xu, Zihan Yan, Sangsu Bang, Dmitry Velmeshev, Ru-Rong Ji","doi":"10.1016/j.neuron.2025.01.012","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.01.012","url":null,"abstract":"Astrocytes in the spinal cord dorsal horn (SDH) play a pivotal role in synaptic transmission and neuropathic pain. However, the precise classification of SDH astrocytes in health and disease remains elusive. Here, we reveal Gpr37l1 as a marker and functional regulator of spinal astrocytes. Through single-nucleus RNA sequencing, we identified Gpr37l1 as a selective G-protein-coupled receptor (GPCR) marker for spinal cord astrocytes. Notably, SDH displayed reactive astrocyte phenotypes and exacerbated neuropathic pain following nerve injury combined with Gpr37l1 deficiency. In naive animals, Gpr37l1 knockdown in SDH astrocytes induces astrogliosis and pain hypersensitivity, while Gpr37l1-/- mice fail to recover from neuropathic pain. GPR37L1 activation by maresin 1 increased astrocyte glutamate transporter 1 (GLT-1) activity and reduced spinal EPSCs and neuropathic pain. Selective overexpression of Gpr37l1 in SDH astrocytes reversed neuropathic pain and astrogliosis after nerve injury. Our findings illuminate astrocyte GPR37l1 as an essential negative regulator of pain, which protects against neuropathic pain through astrocyte signaling in SDH.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425852","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 TMC1 and TMC2 are mechanically gated ion channels. 人类 TMC1 和 TMC2 是机械门控离子通道。

IF 14.7 1区医学

Neuron Pub Date : 2025-02-05 Epub Date: 2024-12-13 DOI: 10.1016/j.neuron.2024.11.009

Songdi Fu, Xueqi Pan, Mingshun Lu, Jianying Dong, Zhiqiang Yan

引用次数: 0

Non-image-forming photoreceptors improve visual orientation selectivity and image perception. 非成像光感受器改善视觉定向选择性和图像感知。

IF 14.7 1区医学

Neuron Pub Date : 2025-02-05 Epub Date: 2024-12-17 DOI: 10.1016/j.neuron.2024.11.015

Yiming Shi, Jiaming Zhang, Xingyi Li, Yuchong Han, Jiangheng Guan, Yilin Li, Jiawei Shen, Tzvetomir Tzvetanov, Dongyu Yang, Xinyi Luo, Yichuan Yao, Zhikun Chu, Tianyi Wu, Zhiping Chen, Ying Miao, Yufei Li, Qian Wang, Jiaxi Hu, Jianjun Meng, Xiang Liao, Yifeng Zhou, Louis Tao, Yuqian Ma, Jutao Chen, Mei Zhang, Rong Liu, Yuanyuan Mi, Jin Bao, Zhong Li, Xiaowei Chen, Tian Xue

{"title":"Non-image-forming photoreceptors improve visual orientation selectivity and image perception.","authors":"Yiming Shi, Jiaming Zhang, Xingyi Li, Yuchong Han, Jiangheng Guan, Yilin Li, Jiawei Shen, Tzvetomir Tzvetanov, Dongyu Yang, Xinyi Luo, Yichuan Yao, Zhikun Chu, Tianyi Wu, Zhiping Chen, Ying Miao, Yufei Li, Qian Wang, Jiaxi Hu, Jianjun Meng, Xiang Liao, Yifeng Zhou, Louis Tao, Yuqian Ma, Jutao Chen, Mei Zhang, Rong Liu, Yuanyuan Mi, Jin Bao, Zhong Li, Xiaowei Chen, Tian Xue","doi":"10.1016/j.neuron.2024.11.015","DOIUrl":"10.1016/j.neuron.2024.11.015","url":null,"abstract":"It has long been a decades-old dogma that image perception is mediated solely by rods and cones, while intrinsically photosensitive retinal ganglion cells (ipRGCs) are responsible only for non-image-forming vision, such as circadian photoentrainment and pupillary light reflexes. Surprisingly, we discovered that ipRGC activation enhances the orientation selectivity of layer 2/3 neurons in the primary visual cortex (V1) of mice by both increasing preferred-orientation responses and narrowing tuning bandwidth. Mechanistically, we found that the tuning properties of V1 excitatory and inhibitory neurons are differentially influenced by ipRGC activation, leading to a reshaping of the excitatory/inhibitory balance that enhances visual cortical orientation selectivity. Furthermore, light activation of ipRGCs improves behavioral orientation discrimination in mice. Importantly, we found that specific activation of ipRGCs in human participants through visual spectrum manipulation significantly enhances visual orientation discriminability. Our study reveals a visual channel originating from \"non-image-forming photoreceptors\" that facilitates visual orientation feature perception.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"486-500.e13"},"PeriodicalIF":14.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854701","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 and segregated cortical circuits control winning and losing behaviors.

IF 14.7 1区医学

Neuron Pub Date : 2025-02-05 DOI: 10.1016/j.neuron.2025.01.007

Elizabeth Illescas-Huerta, Nancy Padilla-Coreano

引用次数: 0

Reconstructing a new hippocampal engram for systems reconsolidation and remote memory updating. 重建新的海马体印记图用于系统再巩固和远程记忆更新。

IF 14.7 1区医学

Neuron Pub Date : 2025-02-05 Epub Date: 2024-12-16 DOI: 10.1016/j.neuron.2024.11.010

Bo Lei, Bilin Kang, Yuejun Hao, Haoyu Yang, Zihan Zhong, Zihan Zhai, Yi Zhong

{"title":"Reconstructing a new hippocampal engram for systems reconsolidation and remote memory updating.","authors":"Bo Lei, Bilin Kang, Yuejun Hao, Haoyu Yang, Zihan Zhong, Zihan Zhai, Yi Zhong","doi":"10.1016/j.neuron.2024.11.010","DOIUrl":"10.1016/j.neuron.2024.11.010","url":null,"abstract":"Recalling systems-consolidated neocortex-dependent remote memories re-engages the hippocampus in a process called systems reconsolidation. However, underlying mechanisms, particularly for the origin of the reinstated hippocampal memory engram, remain elusive. By developing a triple-event labeling tool and employing two-photon imaging, we trace hippocampal engram ensembles from memory acquisition to systems reconsolidation and find that remote recall recruits a new engram ensemble in the hippocampus for subsequent memory retrieval. Consistently, recruiting new engrams is supported by adult hippocampal neurogenesis-mediated silencing of original engrams. This new engram ensemble receives currently experienced contextual information, incorporates new information into the remote memory, and supports remote memory updating. Such a reconstructed hippocampal memory is then integrated with the valence of remote memory via medial prefrontal cortex projection-mediated activity coordination between the hippocampus and amygdala. Thus, the reconstruction of new memory engrams underlies systems reconsolidation, which explains how remote memories are updated with new information.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"471-485.e6"},"PeriodicalIF":14.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847143","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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