IF 14.7 1区医学

Neuron Pub Date : 2024-10-23 DOI: 10.1016/j.neuron.2024.10.001

Haining Zhu

引用次数: 0

A bimodal taxonomy of adult human brain sulcal morphology related to timing of fetal sulcation and trans-sulcal gene expression gradients. 与胎儿脑沟形成时间和跨脑沟基因表达梯度有关的成人脑沟形态双模分类法。

IF 14.7 1区医学

Neuron Pub Date : 2024-10-23 Epub Date: 2024-08-22 DOI: 10.1016/j.neuron.2024.07.023

William E Snyder, Petra E Vértes, Vanessa Kyriakopoulou, Konrad Wagstyl, Logan Z J Williams, Dustin Moraczewski, Adam G Thomas, Vyacheslav R Karolis, Jakob Seidlitz, Denis Rivière, Emma C Robinson, Jean-Francois Mangin, Armin Raznahan, Edward T Bullmore

{"title":"A bimodal taxonomy of adult human brain sulcal morphology related to timing of fetal sulcation and trans-sulcal gene expression gradients.","authors":"William E Snyder, Petra E Vértes, Vanessa Kyriakopoulou, Konrad Wagstyl, Logan Z J Williams, Dustin Moraczewski, Adam G Thomas, Vyacheslav R Karolis, Jakob Seidlitz, Denis Rivière, Emma C Robinson, Jean-Francois Mangin, Armin Raznahan, Edward T Bullmore","doi":"10.1016/j.neuron.2024.07.023","DOIUrl":"10.1016/j.neuron.2024.07.023","url":null,"abstract":"We developed a computational pipeline (now provided as a resource) for measuring morphological similarity between cortical surface sulci to construct a sulcal phenotype network (SPN) from each magnetic resonance imaging (MRI) scan in an adult cohort (n = 34,725; 45-82 years). Networks estimated from pairwise similarities of 40 sulci on 5 morphological metrics comprised two clusters of sulci, represented also by the bimodal distribution of sulci on a linear-to-complex dimension. Linear sulci were more heritable and typically located in unimodal cortex, and complex sulci were less heritable and typically located in heteromodal cortex. Aligning these results with an independent fetal brain MRI cohort (n = 228; 21-36 gestational weeks), we found that linear sulci formed earlier, and the earliest and latest-forming sulci had the least between-adult variation. Using high-resolution maps of cortical gene expression, we found that linear sulcation is mechanistically underpinned by trans-sulcal gene expression gradients enriched for developmental processes.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"3396-3411.e6"},"PeriodicalIF":14.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046953","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

Disruption of nuclear speckle integrity dysregulates RNA splicing in C9ORF72-FTD/ALS. 核斑点完整性的破坏使 C9ORF72-FTD/ALS 中的 RNA 剪接失调。

IF 14.7 1区医学

Neuron Pub Date : 2024-10-23 Epub Date: 2024-08-23 DOI: 10.1016/j.neuron.2024.07.025

Rong Wu, Yingzhi Ye, Daoyuan Dong, Zhe Zhang, Shaopeng Wang, Yini Li, Noelle Wright, Javier Redding-Ochoa, Koping Chang, Shaohai Xu, Xueting Tu, Chengzhang Zhu, Lyle W Ostrow, Xavier Roca, Juan C Troncoso, Bin Wu, Shuying Sun

{"title":"Disruption of nuclear speckle integrity dysregulates RNA splicing in C9ORF72-FTD/ALS.","authors":"Rong Wu, Yingzhi Ye, Daoyuan Dong, Zhe Zhang, Shaopeng Wang, Yini Li, Noelle Wright, Javier Redding-Ochoa, Koping Chang, Shaohai Xu, Xueting Tu, Chengzhang Zhu, Lyle W Ostrow, Xavier Roca, Juan C Troncoso, Bin Wu, Shuying Sun","doi":"10.1016/j.neuron.2024.07.025","DOIUrl":"10.1016/j.neuron.2024.07.025","url":null,"abstract":"Expansion of an intronic (GGGGCC)n repeat within the C9ORF72 gene is the most common genetic cause of both frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) (C9-FTD/ALS), characterized with aberrant repeat RNA foci and noncanonical translation-produced dipeptide repeat (DPR) protein inclusions. Here, we elucidate that the (GGGGCC)n repeat RNA co-localizes with nuclear speckles and alters their phase separation properties and granule dynamics. Moreover, the essential nuclear speckle scaffold protein SRRM2 is sequestered into the poly-GR cytoplasmic inclusions in the C9-FTD/ALS mouse model and patient postmortem tissues, exacerbating the nuclear speckle dysfunction. Impaired nuclear speckle integrity induces global exon skipping and intron retention in human iPSC-derived neurons and causes neuronal toxicity. Similar alternative splicing changes can be found in C9-FTD/ALS patient postmortem tissues. This work identified novel molecular mechanisms of global RNA splicing defects caused by impaired nuclear speckle function in C9-FTD/ALS and revealed novel potential biomarkers or therapeutic targets.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"3434-3451.e11"},"PeriodicalIF":14.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056189","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

Human assembloids reveal the consequences of CACNA1G gene variants in the thalamocortical pathway. 人类集合体揭示了丘脑皮层通路中 CACNA1G 基因变异的后果。

IF 14.7 1区医学

Neuron Pub Date : 2024-10-16 DOI: 10.1016/j.neuron.2024.09.020

Ji-Il Kim, Yuki Miura, Min-Yin Li, Omer Revah, Sridhar Selvaraj, Fikri Birey, Xiangling Meng, Mayuri Vijay Thete, Sergey D Pavlov, Jimena Andersen, Anca M Pașca, Matthew H Porteus, John R Huguenard, Sergiu P Pașca

{"title":"Human assembloids reveal the consequences of CACNA1G gene variants in the thalamocortical pathway.","authors":"Ji-Il Kim, Yuki Miura, Min-Yin Li, Omer Revah, Sridhar Selvaraj, Fikri Birey, Xiangling Meng, Mayuri Vijay Thete, Sergey D Pavlov, Jimena Andersen, Anca M Pașca, Matthew H Porteus, John R Huguenard, Sergiu P Pașca","doi":"10.1016/j.neuron.2024.09.020","DOIUrl":"10.1016/j.neuron.2024.09.020","url":null,"abstract":"Abnormalities in thalamocortical crosstalk can lead to neuropsychiatric disorders. Variants in CACNA1G, which encodes the α1G subunit of the thalamus-enriched T-type calcium channel, are associated with absence seizures, intellectual disability, and schizophrenia, but the cellular and circuit consequences of these genetic variants in humans remain unknown. Here, we developed a human assembloid model of the thalamocortical pathway to dissect the contribution of genetic variants in T-type calcium channels. We discovered that the M1531V CACNA1G variant associated with seizures led to changes in T-type currents in thalamic neurons, as well as correlated hyperactivity of thalamic and cortical neurons in assembloids. By contrast, CACNA1G loss, which has been associated with risk of schizophrenia, resulted in abnormal thalamocortical connectivity that was related to both increased spontaneous thalamic activity and aberrant axonal projections. These results illustrate the utility of multi-cellular systems for interrogating human genetic disease risk variants at both cellular and circuit level.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471083","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

Spatial context non-uniformly modulates inter-laminar information flow in the primary visual cortex. 空间情境非均匀地调节初级视觉皮层的层间信息流

IF 14.7 1区医学

Neuron Pub Date : 2024-10-15 DOI: 10.1016/j.neuron.2024.09.021

Xize Xu, Mitchell P Morton, Sachira Denagamage, Nyomi V Hudson, Anirvan S Nandy, Monika P Jadi

{"title":"Spatial context non-uniformly modulates inter-laminar information flow in the primary visual cortex.","authors":"Xize Xu, Mitchell P Morton, Sachira Denagamage, Nyomi V Hudson, Anirvan S Nandy, Monika P Jadi","doi":"10.1016/j.neuron.2024.09.021","DOIUrl":"10.1016/j.neuron.2024.09.021","url":null,"abstract":"Our visual experience is a result of the concerted activity of neuronal ensembles in the sensory hierarchy. Yet, how the spatial organization of objects influences this activity remains poorly understood. We investigate how inter-laminar information flow within the primary visual cortex (V1) is affected by visual stimuli in isolation or with flankers at spatial configurations that are known to cause non-uniform degradation of perception. By employing dimensionality reduction approaches to simultaneous, layer-specific population recordings, we establish that information propagation between cortical layers occurs along a structurally stable communication subspace. The spatial configuration of contextual stimuli differentially modulates inter-laminar communication efficacy, the balance of feedforward and effective feedback signaling, and contextual signaling in the superficial layers. Remarkably, these modulations mirror the spatially non-uniform aspects of perceptual degradation. Our results suggest a model of retinotopically non-uniform cortical connectivity in the output layers of V1 that influences information flow in the sensory hierarchy.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504952","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

Accurate neural control of a hand prosthesis by posture-related activity in the primate grasping circuit. 通过灵长类动物抓握回路中与姿势相关的活动对假手进行精确的神经控制。

IF 14.7 1区医学

Neuron Pub Date : 2024-10-14 DOI: 10.1016/j.neuron.2024.09.018

Andres Agudelo-Toro, Jonathan A Michaels, Wei-An Sheng, Hansjörg Scherberger

引用次数: 0

Central control of opioid-induced mechanical hypersensitivity and tolerance in mice. 中枢控制阿片诱导的小鼠机械过敏性和耐受性。

IF 14.7 1区医学

Neuron Pub Date : 2024-10-12 DOI: 10.1016/j.neuron.2024.09.014

Guangjuan Yin, Kaifang Duan, Dong Dong, Feng Du, Chao Guo, Changyi Zhang, Xi Liu, Yuanjie Sun, Tianwen Huang, Guangfu Cui, Longzhen Cheng

{"title":"Central control of opioid-induced mechanical hypersensitivity and tolerance in mice.","authors":"Guangjuan Yin, Kaifang Duan, Dong Dong, Feng Du, Chao Guo, Changyi Zhang, Xi Liu, Yuanjie Sun, Tianwen Huang, Guangfu Cui, Longzhen Cheng","doi":"10.1016/j.neuron.2024.09.014","DOIUrl":"https://doi.org/10.1016/j.neuron.2024.09.014","url":null,"abstract":"Repetitive use of morphine (MF) and other opioids can trigger two major pain-related side effects: opioid-induced hypersensitivity (OIH) and analgesic tolerance, which can be subclassified as mechanical and thermal. The central mechanisms underlying mechanical OIH/tolerance remain unresolved. Here, we report that a brain-to-spinal opioid pathway, starting from μ-opioid receptor (MOR)-expressing neuron in the lateral parabrachial nucleus (lPBNMOR+) via dynorphin (Dyn) neuron in the paraventricular hypothalamic nucleus (PVHDyn+) to κ-opioid receptor (KOR)-expressing GABAergic neuron in the spinal dorsal horn (SDHKOR-GABA), controls repeated systemic administration of MF-induced mechanical OIH and tolerance in mice. The above effect is likely mediated by disruption of dorsal horn gate control for MF-resistant mechanical pain via silencing of the Dyn-positive GABAergic neurons in the SDH (lPBNMOR+ → PVHDyn+ → SDHKOR-GABA → SDHDyn-GABA). Repetitive binding of MF to MORs during repeated MF administration disrupted the above circuits. Targeting the above brain-to-spinal opioid pathways rescued repetitive MF-induced mechanical OIH and tolerance.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471082","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

Persistent activity during working memory maintenance predicts long-term memory formation in the human hippocampus. 工作记忆维持过程中的持续活动可预测人类海马体的长期记忆形成。

IF 14.7 1区医学

Neuron Pub Date : 2024-10-10 DOI: 10.1016/j.neuron.2024.09.013

Jonathan Daume, Jan Kamiński, Yousef Salimpour, Andrea Gómez Palacio Schjetnan, William S Anderson, Taufik A Valiante, Adam N Mamelak, Ueli Rutishauser

引用次数: 0

Insights into mechanisms and therapeutic avenues for primary familial brain calcification. 原发性家族性脑部钙化的机制和治疗途径透视。

IF 14.7 1区医学

Neuron Pub Date : 2024-10-09 DOI: 10.1016/j.neuron.2024.09.019

Christer Betsholtz

引用次数: 0

Structural basis of psychedelic LSD recognition at dopamine D₁ receptor. 多巴胺 D1 受体识别迷幻剂 LSD 的结构基础。

IF 14.7 1区医学

Neuron Pub Date : 2024-10-09 Epub Date: 2024-08-01 DOI: 10.1016/j.neuron.2024.07.003

Luyu Fan, Youwen Zhuang, Hongyu Wu, Huiqiong Li, Youwei Xu, Yue Wang, Licong He, Shishan Wang, Zhangcheng Chen, Jianjun Cheng, H Eric Xu, Sheng Wang

{"title":"Structural basis of psychedelic LSD recognition at dopamine D1 receptor.","authors":"Luyu Fan, Youwen Zhuang, Hongyu Wu, Huiqiong Li, Youwei Xu, Yue Wang, Licong He, Shishan Wang, Zhangcheng Chen, Jianjun Cheng, H Eric Xu, Sheng Wang","doi":"10.1016/j.neuron.2024.07.003","DOIUrl":"10.1016/j.neuron.2024.07.003","url":null,"abstract":"Understanding the kinetics of LSD in receptors and subsequent induced signaling is crucial for comprehending both the psychoactive and therapeutic effects of LSD. Despite extensive research on LSD's interactions with serotonin 2A and 2B receptors, its behavior on other targets, including dopamine receptors, has remained elusive. Here, we present cryo-EM structures of LSD/PF6142-bound dopamine D1 receptor (DRD1)-legobody complexes, accompanied by a β-arrestin-mimicking nanobody, NBA3, shedding light on the determinants of G protein coupling versus β-arrestin coupling. Structural analysis unveils a distinctive binding mode of LSD in DRD1, particularly with the ergoline moiety oriented toward TM4. Kinetic investigations uncover an exceptionally rapid dissociation rate of LSD in DRD1, attributed to the flexibility of extracellular loop 2 (ECL2). Moreover, G protein can stabilize ECL2 conformation, leading to a significant slowdown in ligand's dissociation rate. These findings establish a solid foundation for further exploration of G protein-coupled receptor (GPCR) dynamics and their relevance to signal transduction.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"3295-3310.e8"},"PeriodicalIF":14.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879205","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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