IF 14.7 1区医学

Neuron Pub Date : 2025-02-05 DOI: 10.1016/j.neuron.2025.01.003

Ali Golbabaei, Paul W Frankland

引用次数: 0

Differential behavioral engagement of inhibitory interneuron subtypes in the zebra finch brain. 抑制性中间神经元亚型在斑胸草雀大脑中的差异行为参与。

IF 14.7 1区医学

Neuron Pub Date : 2025-02-05 Epub Date: 2024-12-06 DOI: 10.1016/j.neuron.2024.11.003

Ellie Hozhabri, Ariadna Corredera Asensio, Margot Elmaleh, Jeong Woo Kim, Matthew B Phillips, Paul W Frazel, Jordane Dimidschstein, Gord Fishell, Michael A Long

{"title":"Differential behavioral engagement of inhibitory interneuron subtypes in the zebra finch brain.","authors":"Ellie Hozhabri, Ariadna Corredera Asensio, Margot Elmaleh, Jeong Woo Kim, Matthew B Phillips, Paul W Frazel, Jordane Dimidschstein, Gord Fishell, Michael A Long","doi":"10.1016/j.neuron.2024.11.003","DOIUrl":"10.1016/j.neuron.2024.11.003","url":null,"abstract":"Inhibitory interneurons are highly heterogeneous circuit elements often characterized by cell biological properties, but how these factors relate to specific roles underlying complex behavior remains poorly understood. Using chronic silicon probe recordings, we demonstrate that distinct interneuron groups perform different inhibitory roles within HVC, a song production circuit in the zebra finch forebrain. To link these functional subtypes to molecular identity, we performed two-photon targeted electrophysiological recordings of HVC interneurons followed by post hoc immunohistochemistry of subtype-specific markers. We find that parvalbumin-expressing interneurons are highly modulated by sensory input and likely mediate auditory gating, whereas a more heterogeneous set of somatostatin-expressing interneurons can strongly regulate activity based on arousal. Using this strategy, we uncover important cell-type-specific network functions in the context of an ethologically relevant motor skill.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"460-470.e7"},"PeriodicalIF":14.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791574","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

A top-down search for inhibitory cell subtypes in the songbird.

IF 14.7 1区医学

Neuron Pub Date : 2025-02-05 DOI: 10.1016/j.neuron.2025.01.009

Todd W Troyer

引用次数: 0

Acute MeCP2 loss in adult mice reveals transcriptional and chromatin changes that precede neurological dysfunction and inform pathogenesis. 成年小鼠急性MeCP2缺失揭示了神经功能障碍之前的转录和染色质变化，并为其发病机制提供信息。

IF 14.7 1区医学

Neuron Pub Date : 2025-02-05 Epub Date: 2024-12-16 DOI: 10.1016/j.neuron.2024.11.006

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":"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":"380-395.e8"},"PeriodicalIF":14.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802321/pdf/","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":"OA","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. 氯胺酮诱导去甲肾上腺素-星形胶质回路的可塑性，从而促进行为的持久性。

IF 14.7 1区医学

Neuron Pub Date : 2025-02-05 Epub Date: 2024-12-17 DOI: 10.1016/j.neuron.2024.11.011

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":"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":"426-443.e5"},"PeriodicalIF":14.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889991/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deconstructing the neural circuit underlying social hierarchy in mice. 解构小鼠社会等级的神经回路。

IF 14.7 1区医学

Neuron Pub Date : 2025-02-05 Epub Date: 2024-12-10 DOI: 10.1016/j.neuron.2024.11.007

Qiuhong Xin, Diyang Zheng, Tingting Zhou, Jiayi Xu, Zheyi Ni, Hailan Hu

{"title":"Deconstructing the neural circuit underlying social hierarchy in mice.","authors":"Qiuhong Xin, Diyang Zheng, Tingting Zhou, Jiayi Xu, Zheyi Ni, Hailan Hu","doi":"10.1016/j.neuron.2024.11.007","DOIUrl":"10.1016/j.neuron.2024.11.007","url":null,"abstract":"Social competition determines hierarchical social status, which profoundly influences animals' behavior and health. The dorsomedial prefrontal cortex (dmPFC) plays a fundamental role in regulating social competitions, but it was unclear how the dmPFC orchestrates win- and lose-related behaviors through its downstream neural circuits. Here, through whole-brain c-Fos mapping, fiber photometry, and optogenetics- or chemogenetics-based manipulations, we identified anatomically segregated win- and lose-related neural pathways downstream of the dmPFC in mice. Specifically, layer 5 neurons projecting to the dorsal raphe nucleus (DRN) and periaqueductal gray (PAG) promote social competition, whereas layer 2/3 neurons projecting to the anterior basolateral amygdala (aBLA) suppress competition. These two neuronal populations show opposite changes in activity during effortful pushes in competition. In vivo and in vitro electrophysiology recordings revealed inhibition from the lose-related pathway to the win-related pathway. Such antagonistic interplay may represent a central principle in how the mPFC orchestrates complex behaviors through top-down control.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"444-459.e7"},"PeriodicalIF":14.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813744","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

Somatic CAG-repeat expansion drives neuronal loss in Huntington's disease.

IF 14.7 1区医学

Neuron Pub Date : 2025-02-05 DOI: 10.1016/j.neuron.2025.01.008

Gillian P Bates

引用次数: 0

snRNA-seq stratifies multiple sclerosis patients into distinct white matter glial responses. snRNA-seq将多发性硬化症患者分层为不同的白质胶质反应。

IF 14.7 1区医学

Neuron Pub Date : 2025-02-05 Epub Date: 2024-12-20 DOI: 10.1016/j.neuron.2024.11.016

Will Macnair, Daniela Calini, Eneritz Agirre, Julien Bryois, Sarah Jäkel, Rebecca Sherrard Smith, Petra Kukanja, Nadine Stokar-Regenscheit, Virginie Ott, Lynette C Foo, Ludovic Collin, Sven Schippling, Eduard Urich, Erik Nutma, Manuel Marzin, Federico Ansaloni, Sandra Amor, Roberta Magliozzi, Elyas Heidari, Mark D Robinson, Charles Ffrench-Constant, Gonçalo Castelo-Branco, Anna Williams, Dheeraj Malhotra

{"title":"snRNA-seq stratifies multiple sclerosis patients into distinct white matter glial responses.","authors":"Will Macnair, Daniela Calini, Eneritz Agirre, Julien Bryois, Sarah Jäkel, Rebecca Sherrard Smith, Petra Kukanja, Nadine Stokar-Regenscheit, Virginie Ott, Lynette C Foo, Ludovic Collin, Sven Schippling, Eduard Urich, Erik Nutma, Manuel Marzin, Federico Ansaloni, Sandra Amor, Roberta Magliozzi, Elyas Heidari, Mark D Robinson, Charles Ffrench-Constant, Gonçalo Castelo-Branco, Anna Williams, Dheeraj Malhotra","doi":"10.1016/j.neuron.2024.11.016","DOIUrl":"10.1016/j.neuron.2024.11.016","url":null,"abstract":"Poor understanding of the cellular and molecular basis of clinical and genetic heterogeneity in progressive multiple sclerosis (MS) has hindered the search for new effective therapies. To address this gap, we analyzed 632,000 single-nucleus RNA sequencing profiles from 156 brain tissue samples of MS and control donors to examine inter- and intra-donor heterogeneity. We found distinct cell type-specific gene expression changes between MS gray and white matter, highlighting clear pathology differences. MS lesion subtypes had different cellular compositions but surprisingly similar cell-type gene expression patterns both within and across patients, suggesting global changes. Most gene expression variability was instead explained by patient effects, allowing us to stratify patients and describe the different pathological processes occurring between patient subgroups. Future mapping of these brain molecular profiles with blood and/or CSF profiles from living MS patients will allow precision medicine approaches anchored in patient-specific pathological processes.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"396-410.e9"},"PeriodicalIF":14.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872671","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

Toward curing neurological autoimmune disorders: Biomarkers, immunological mechanisms, and therapeutic targets. 治疗神经自身免疫性疾病：生物标志物、免疫机制和治疗靶点。

IF 14.7 1区医学

Neuron Pub Date : 2025-02-05 Epub Date: 2025-01-13 DOI: 10.1016/j.neuron.2024.12.006

Yahel Segal, John Soltys, Benjamin D S Clarkson, Charles L Howe, Sarosh R Irani, Sean J Pittock

{"title":"Toward curing neurological autoimmune disorders: Biomarkers, immunological mechanisms, and therapeutic targets.","authors":"Yahel Segal, John Soltys, Benjamin D S Clarkson, Charles L Howe, Sarosh R Irani, Sean J Pittock","doi":"10.1016/j.neuron.2024.12.006","DOIUrl":"10.1016/j.neuron.2024.12.006","url":null,"abstract":"Autoimmune neurology is a rapidly expanding field driven by the discovery of neuroglial autoantibodies and encompassing a myriad of conditions affecting every level of the nervous system. Traditionally, autoantibodies targeting intracellular antigens are considered markers of T cell-mediated cytotoxicity, while those targeting extracellular antigens are viewed as pathogenic drivers of disease. However, recent advances highlight complex interactions between these immune mechanisms, suggesting a continuum of immunopathogenesis. The breakdown of immune tolerance, central to these conditions, is affected by modifiable and non-modifiable risk factors such as genetic predisposition, infections, and malignancy. While significant therapeutic advancements have revolutionized treatment of certain diseases, such as neuromyelitis optica, our understanding of many others, particularly T cell-mediated conditions, remains limited, with fewer treatment options available. Future research should focus on improving effector function modeling and deepening our understanding of the factors influencing immune tolerance, with the goal of providing novel treatment options and improving patient care.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"345-379"},"PeriodicalIF":14.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984347","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

A tale of two algorithms: Structured slots explain prefrontal sequence memory and are unified with hippocampal cognitive maps. 两种算法的故事：结构化槽解释了前额叶序列记忆，并与海马认知图谱相统一。

IF 14.7 1区医学

Neuron Pub Date : 2025-01-22 Epub Date: 2024-11-21 DOI: 10.1016/j.neuron.2024.10.017

James C R Whittington, William Dorrell, Timothy E J Behrens, Surya Ganguli, Mohamady El-Gaby

{"title":"A tale of two algorithms: Structured slots explain prefrontal sequence memory and are unified with hippocampal cognitive maps.","authors":"James C R Whittington, William Dorrell, Timothy E J Behrens, Surya Ganguli, Mohamady El-Gaby","doi":"10.1016/j.neuron.2024.10.017","DOIUrl":"10.1016/j.neuron.2024.10.017","url":null,"abstract":"Remembering events is crucial to intelligent behavior. Flexible memory retrieval requires a cognitive map and is supported by two key brain systems: hippocampal episodic memory (EM) and prefrontal working memory (WM). Although an understanding of EM is emerging, little is understood of WM beyond simple memory retrieval. We develop a mathematical theory relating the algorithms and representations of EM and WM by unveiling a duality between storing memories in synapses versus neural activity. This results in a formalism of prefrontal WM as structured, controllable neural subspaces (activity slots) representing dynamic cognitive maps without synaptic plasticity. Using neural networks, we elucidate differences, similarities, and trade-offs between the hippocampal and prefrontal algorithms. Lastly, we show that prefrontal representations in tasks from list learning to cue-dependent recall are unified as controllable activity slots. Our results unify frontal and temporal representations of memory and offer a new understanding for dynamic prefrontal representations of WM.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"321-333.e6"},"PeriodicalIF":14.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693227","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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