IF 14.7 1区医学

Neuron Pub Date : 2024-12-18 Epub Date: 2024-10-31 DOI: 10.1016/j.neuron.2024.10.007

Norah Al-Azzam, Jenny H To, Vaishali Gautam, Lena A Street, Chloe B Nguyen, Jack T Naritomi, Dylan C Lam, Assael A Madrigal, Benjamin Lee, Wenhao Jin, Anthony Avina, Orel Mizrahi, Jasmine R Mueller, Willard Ford, Cara R Schiavon, Elena Rebollo, Anthony Q Vu, Steven M Blue, Yashwin L Madakamutil, Uri Manor, Jeffrey D Rothstein, Alyssa N Coyne, Marko Jovanovic, Gene W Yeo

{"title":"Inhibition of RNA splicing triggers CHMP7 nuclear entry, impacting TDP-43 function and leading to the onset of ALS cellular phenotypes.","authors":"Norah Al-Azzam, Jenny H To, Vaishali Gautam, Lena A Street, Chloe B Nguyen, Jack T Naritomi, Dylan C Lam, Assael A Madrigal, Benjamin Lee, Wenhao Jin, Anthony Avina, Orel Mizrahi, Jasmine R Mueller, Willard Ford, Cara R Schiavon, Elena Rebollo, Anthony Q Vu, Steven M Blue, Yashwin L Madakamutil, Uri Manor, Jeffrey D Rothstein, Alyssa N Coyne, Marko Jovanovic, Gene W Yeo","doi":"10.1016/j.neuron.2024.10.007","DOIUrl":"10.1016/j.neuron.2024.10.007","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is linked to the reduction of certain nucleoporins in neurons. Increased nuclear localization of charged multivesicular body protein 7 (CHMP7), a protein involved in nuclear pore surveillance, has been identified as a key factor damaging nuclear pores and disrupting transport. Using CRISPR-based microRaft, followed by gRNA identification (CRaft-ID), we discovered 55 RNA-binding proteins (RBPs) that influence CHMP7 localization, including SmD1, a survival of motor neuron (SMN) complex component. Immunoprecipitation-mass spectrometry (IP-MS) and enhanced crosslinking and immunoprecipitation (CLIP) analyses revealed CHMP7's interactions with SmD1, small nuclear RNAs, and splicing factor mRNAs in motor neurons (MNs). ALS induced pluripotent stem cell (iPSC)-MNs show reduced SmD1 expression, and inhibiting SmD1/SMN complex increased CHMP7 nuclear localization. Crucially, overexpressing SmD1 in ALS iPSC-MNs restored CHMP7's cytoplasmic localization and corrected STMN2 splicing. Our findings suggest that early ALS pathogenesis is driven by SMN complex dysregulation.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"4033-4047.e8"},"PeriodicalIF":14.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564842","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 neurobiology of thirst and salt appetite.

IF 14.7 1区医学

Neuron Pub Date : 2024-12-18 Epub Date: 2024-11-27 DOI: 10.1016/j.neuron.2024.10.028

James C R Grove, Zachary A Knight

引用次数: 0

Glioblastoma functional heterogeneity and enrichment of cancer stem cells with tumor recurrence. 胶质母细胞瘤功能异质性和肿瘤干细胞富集与肿瘤复发的关系

IF 14.7 1区医学

Neuron Pub Date : 2024-12-18 Epub Date: 2024-11-06 DOI: 10.1016/j.neuron.2024.10.012

Xuanhua P Xie, Mungunsarnai Ganbold, Jing Li, Michelle Lien, Mollie E Chipman, Tao Wang, Chenura D Jayewickreme, Alicia M Pedraza, Tejus Bale, Viviane Tabar, Cameron Brennan, Daochun Sun, Roshan Sharma, Luis F Parada

{"title":"Glioblastoma functional heterogeneity and enrichment of cancer stem cells with tumor recurrence.","authors":"Xuanhua P Xie, Mungunsarnai Ganbold, Jing Li, Michelle Lien, Mollie E Chipman, Tao Wang, Chenura D Jayewickreme, Alicia M Pedraza, Tejus Bale, Viviane Tabar, Cameron Brennan, Daochun Sun, Roshan Sharma, Luis F Parada","doi":"10.1016/j.neuron.2024.10.012","DOIUrl":"10.1016/j.neuron.2024.10.012","url":null,"abstract":"Glioblastoma (GBM) is an incurable disease with high intratumoral heterogeneity. Bioinformatic studies have examined transcriptional heterogeneity with differing conclusions. Here, we characterize GBM heterogeneity and highlight critical phenotypic and hierarchical roles for quiescent cancer stem cells (qCSCs). Unsupervised single-cell transcriptomic analysis of patient-derived xenografts (PDXs) delineates six GBM transcriptional states with unique tumor exclusive gene signatures, five of which display congruence with central nervous system (CNS) cell lineages. We employ a surrogate tumor evolution assay by serial xenograft transplantation to demonstrate faithful preservation of somatic mutations, transcriptome, and qCSCs. PDX chemotherapy results in CSC resistance and expansion, also seen in recurrent patient GBM. In aggregate, these novel GBM transcriptional signatures exclusively identify tumor cells and define the hierarchical landscape as stable biologically discernible cell types that allow capture of their evolution upon recurrence, emphasizing the importance of CSCs and demonstrating general relevance to all GBM.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"4017-4032.e6"},"PeriodicalIF":14.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604601","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

Zero-shot counting with a dual-stream neural network model. 利用双流神经网络模型进行零点计数。

IF 14.7 1区医学

Neuron Pub Date : 2024-12-18 Epub Date: 2024-11-01 DOI: 10.1016/j.neuron.2024.10.008

Jessica A F Thompson, Hannah Sheahan, Tsvetomira Dumbalska, Julian D Sandbrink, Manuela Piazza, Christopher Summerfield

引用次数: 0

Non-image-forming photoreceptors improve visual orientation selectivity and image perception.

IF 14.7 1区医学

Neuron Pub 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":"https://doi.org/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":""},"PeriodicalIF":14.7,"publicationDate":"2024-12-17","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

Ketamine induces plasticity in a norepinephrine-astroglial circuit to promote behavioral perseverance.

IF 14.7 1区医学

Neuron Pub Date : 2024-12-16 DOI: 10.1016/j.neuron.2024.11.011

Marc Duque, Alex B Chen, Eric Hsu, Sujatha Narayan, Altyn Rymbek, Shahinoor Begum, Gesine Saher, Adam E Cohen, David E Olson, Yulong Li, David A Prober, Dwight E Bergles, Mark C Fishman, Florian Engert, Misha B Ahrens

{"title":"Ketamine induces plasticity in a norepinephrine-astroglial circuit to promote behavioral perseverance.","authors":"Marc Duque, Alex B Chen, Eric Hsu, Sujatha Narayan, Altyn Rymbek, Shahinoor Begum, Gesine Saher, Adam E Cohen, David E Olson, Yulong Li, David A Prober, Dwight E Bergles, Mark C Fishman, Florian Engert, Misha B Ahrens","doi":"10.1016/j.neuron.2024.11.011","DOIUrl":"https://doi.org/10.1016/j.neuron.2024.11.011","url":null,"abstract":"Transient exposure to ketamine can trigger lasting changes in behavior and mood. We found that brief ketamine exposure causes long-term suppression of futility-induced passivity in larval zebrafish, reversing the \"giving-up\" response that normally occurs when swimming fails to cause forward movement. Whole-brain imaging revealed that ketamine hyperactivates the norepinephrine-astroglia circuit responsible for passivity. After ketamine washout, this circuit exhibits hyposensitivity to futility, leading to long-term increased perseverance. Pharmacological, chemogenetic, and optogenetic manipulations show that norepinephrine and astrocytes are necessary and sufficient for ketamine's long-term perseverance-enhancing aftereffects. In vivo calcium imaging revealed that astrocytes in adult mouse cortex are similarly activated during futility in the tail suspension test and that acute ketamine exposure also induces astrocyte hyperactivation. The cross-species conservation of ketamine's modulation of noradrenergic-astroglial circuits and evidence that plasticity in this pathway can alter the behavioral response to futility hold promise for identifying new strategies to treat affective disorders.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854698","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

Reconstructing a new hippocampal engram for systems reconsolidation and remote memory updating.

IF 14.7 1区医学

Neuron Pub Date : 2024-12-12 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":"https://doi.org/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":""},"PeriodicalIF":14.7,"publicationDate":"2024-12-12","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

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 : 2024-12-11 DOI: 10.1016/j.neuron.2024.11.009

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

引用次数: 0

The unbearable slowness of being: Why do we live at 10 bits/s?

IF 14.7 1区医学

Neuron Pub Date : 2024-12-06 DOI: 10.1016/j.neuron.2024.11.008

Jieyu Zheng, Markus Meister

引用次数: 0

Acute MeCP2 loss in adult mice reveals transcriptional and chromatin changes that precede neurological dysfunction and inform pathogenesis.

IF 14.7 1区医学

Neuron Pub Date : 2024-12-06 DOI: 10.1016/j.neuron.2024.11.006

Sameer S Bajikar, Jian Zhou, Ryan O'Hara, Harini P Tirumala, Mark A Durham, Alexander J Trostle, Michelle Dias, Yingyao Shao, Hu Chen, Wei Wang, Hari Krishna Yalamanchili, Ying-Wooi Wan, Laura A Banaszynski, Zhandong Liu, Huda Y Zoghbi

{"title":"Acute MeCP2 loss in adult mice reveals transcriptional and chromatin changes that precede neurological dysfunction and inform pathogenesis.","authors":"Sameer S Bajikar, Jian Zhou, Ryan O'Hara, Harini P Tirumala, Mark A Durham, Alexander J Trostle, Michelle Dias, Yingyao Shao, Hu Chen, Wei Wang, Hari Krishna Yalamanchili, Ying-Wooi Wan, Laura A Banaszynski, Zhandong Liu, Huda Y Zoghbi","doi":"10.1016/j.neuron.2024.11.006","DOIUrl":"https://doi.org/10.1016/j.neuron.2024.11.006","url":null,"abstract":"Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene cause Rett syndrome, a severe childhood neurological disorder. MeCP2 is a well-established transcriptional repressor, yet upon its loss, hundreds of genes are dysregulated in both directions. To understand what drives such dysregulation, we deleted Mecp2 in adult mice, circumventing developmental contributions and secondary pathogenesis. We performed time series transcriptional, chromatin, and phenotypic analyses of the hippocampus to determine the immediate consequences of MeCP2 loss and the cascade of pathogenesis. We find that loss of MeCP2 causes immediate and bidirectional progressive dysregulation of the transcriptome. To understand what drives gene downregulation, we profiled genome-wide histone modifications and found that a decrease in histone H3 acetylation (ac) at downregulated genes is among the earliest molecular changes occurring well before any measurable deficiencies in electrophysiology and neurological function. These data reveal a molecular cascade that drives disease independent of any developmental contributions or secondary pathogenesis.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847141","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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