IF 14.7 1区医学

Neuron Pub Date : 2025-05-07 DOI: 10.1016/j.neuron.2025.04.010

Amalia Papanikolaou, David Graykowski, Byung Il Lee, Mengke Yang, Robert Ellingford, Jana Zünkler, Suraya A Bond, James M Rowland, Rikesh M Rajani, Samuel S Harris, David J Sharp, Marc Aurel Busche

{"title":"Selectively vulnerable deep cortical layer 5/6 fast-spiking interneurons in Alzheimer's disease models in vivo.","authors":"Amalia Papanikolaou, David Graykowski, Byung Il Lee, Mengke Yang, Robert Ellingford, Jana Zünkler, Suraya A Bond, James M Rowland, Rikesh M Rajani, Samuel S Harris, David J Sharp, Marc Aurel Busche","doi":"10.1016/j.neuron.2025.04.010","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.04.010","url":null,"abstract":"Alzheimer's disease (AD) is initiated by amyloid-beta (Aβ) accumulation in the neocortex; however, the cortical layers and neuronal cell types first susceptible to Aβ remain unknown. Using in vivo two-photon Ca2+ imaging in the visual cortex of AD mouse models, we found that cortical layer 5 neurons displayed abnormally prolonged Ca2+ transients before substantial plaque formation. Neuropixels recordings revealed that these abnormal transients were associated with reduced spiking and impaired visual tuning of parvalbumin (PV)-positive fast-spiking interneurons (FSIs) in layers 5/6, whereas PV-FSIs in superficial layers remained unaffected. These dysfunctions occurred alongside a deep-layer-specific reduction in neuronal pentraxin 2 (NPTX2) within excitatory neurons, decreased GluA4 in PV-FSIs, and fewer excitatory synapses onto PV-FSIs. Notably, NPTX2 overexpression increased excitatory input onto layers 5/6 PV-FSIs and rectified their spiking activity. Thus, our findings reveal an early selective impairment of deep cortical layers 5/6 in AD models and identify deep-layer PV-FSIs as therapeutic targets.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030177","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 transcriptional atlas of gut-innervating neurons reveals activation of interferon signaling and ferroptosis during intestinal inflammation. 肠道神经神经元的转录图谱揭示了肠道炎症期间干扰素信号和铁下垂的激活。

IF 14.7 1区医学

Neuron Pub Date : 2025-05-07 Epub Date: 2025-03-17 DOI: 10.1016/j.neuron.2025.02.018

Patrycja M Forster, Manuel O Jakob, Dilmurat Yusuf, Marvin Bubeck, Heidi Limberger, Yanjiang Luo, Paula Thieme, Alexandra Polici, Nele Sterczyk, Sotiria Boulekou, Laura Bartel, Catalina Cosovanu, Mario Witkowski, Miguel González-Acera, Anja A Kühl, Carl Weidinger, Rolf Backofen, Ahmed N Hegazy, Jay V Patankar, Christoph S N Klose

{"title":"A transcriptional atlas of gut-innervating neurons reveals activation of interferon signaling and ferroptosis during intestinal inflammation.","authors":"Patrycja M Forster, Manuel O Jakob, Dilmurat Yusuf, Marvin Bubeck, Heidi Limberger, Yanjiang Luo, Paula Thieme, Alexandra Polici, Nele Sterczyk, Sotiria Boulekou, Laura Bartel, Catalina Cosovanu, Mario Witkowski, Miguel González-Acera, Anja A Kühl, Carl Weidinger, Rolf Backofen, Ahmed N Hegazy, Jay V Patankar, Christoph S N Klose","doi":"10.1016/j.neuron.2025.02.018","DOIUrl":"10.1016/j.neuron.2025.02.018","url":null,"abstract":"Enteric infections often cause long-term sequelae, including persistent gastrointestinal symptoms, such as pain, discomfort, or irritable bowel syndrome. The plethora of sensory symptoms indicates that gut-innervating neurons might be directly affected by inflammation. However, sequencing studies of neurons in the gastrointestinal tract are hampered by difficulties in purifying neurons, especially during inflammation. Activating a nuclear GFP tag selectively in neurons enabled sort purification of intrinsic and extrinsic neurons of the gastrointestinal tract in models of intestinal inflammation. Using bulk and single-nucleus RNA sequencing, we mapped the whole transcriptomic landscape and identified a conserved neuronal response to inflammation, which included the interferon signaling and ferroptosis pathway. Deletion of the interferon receptor 1 in neurons regulated ferroptosis, neuronal loss, and consequently gut-transit time. Collectively, this study offers a resource documenting neuronal adaptation to inflammatory conditions and exposes the interferon and ferroptosis pathways as signaling cascades activated in neurons during inflammation.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"1333-1351.e7"},"PeriodicalIF":14.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657967","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 rescues anhedonia by cell-type- and input-specific adaptations in the nucleus accumbens. 氯胺酮通过伏隔核的细胞类型和输入特异性适应来拯救快感缺乏症。

IF 14.7 1区医学

Neuron Pub Date : 2025-05-07 Epub Date: 2025-03-19 DOI: 10.1016/j.neuron.2025.02.021

Federica Lucantonio, Jacob Roeglin, Shuwen Li, Jaden Lu, Aleesha Shi, Katherine Czerpaniak, Francesca R Fiocchi, Leonardo Bontempi, Brenda C Shields, Carlos A Zarate, Michael R Tadross, Marco Pignatelli

{"title":"Ketamine rescues anhedonia by cell-type- and input-specific adaptations in the nucleus accumbens.","authors":"Federica Lucantonio, Jacob Roeglin, Shuwen Li, Jaden Lu, Aleesha Shi, Katherine Czerpaniak, Francesca R Fiocchi, Leonardo Bontempi, Brenda C Shields, Carlos A Zarate, Michael R Tadross, Marco Pignatelli","doi":"10.1016/j.neuron.2025.02.021","DOIUrl":"10.1016/j.neuron.2025.02.021","url":null,"abstract":"Ketamine is recognized as a rapid and sustained antidepressant, particularly for major depression unresponsive to conventional treatments. Anhedonia is a common symptom of depression for which ketamine is highly efficacious, but the underlying circuits and synaptic changes are not well understood. Here, we show that the nucleus accumbens (NAc) is essential for ketamine's effect in rescuing anhedonia in mice subjected to chronic stress. Specifically, a single exposure to ketamine rescues stress-induced decreased strength of excitatory synapses on NAc-D1 dopamine receptor-expressing medium spiny neurons (D1-MSNs). Using a cell-specific pharmacology method, we establish the necessity of this synaptic restoration for the sustained therapeutic effects of ketamine on anhedonia. Examining causal sufficiency, artificially increasing excitatory synaptic strength onto D1-MSNs recapitulates the behavioral amelioration induced by ketamine. Finally, we used opto- and chemogenetic approaches to determine the presynaptic origin of the relevant synapses, implicating monosynaptic inputs from the medial prefrontal cortex and ventral hippocampus.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"1398-1412.e4"},"PeriodicalIF":14.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670176","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

The estrous cycle modulates hippocampal spine dynamics, dendritic processing, and spatial coding. 发情周期调节海马脊柱动力学、树突加工和空间编码。

IF 14.7 1区医学

Neuron Pub Date : 2025-05-07 DOI: 10.1016/j.neuron.2025.04.014

Nora S Wolcott, William T Redman, Marie Karpinska, Emily G Jacobs, Michael J Goard

引用次数: 0

The paraventricular thalamus mediates visceral pain and anxiety-like behaviors via two distinct pathways. 室旁丘脑通过两种不同的途径介导内脏疼痛和焦虑样行为。

IF 14.7 1区医学

Neuron Pub Date : 2025-05-06 DOI: 10.1016/j.neuron.2025.04.019

Di Li, Yong-Chang Li, Zheng-Yan Zhu, Fu-Chao Zhang, Qiu-Ying Zhao, Jia-Hui Jiang, Biyu Shen, Yong Tang, Guang-Yin Xu

{"title":"The paraventricular thalamus mediates visceral pain and anxiety-like behaviors via two distinct pathways.","authors":"Di Li, Yong-Chang Li, Zheng-Yan Zhu, Fu-Chao Zhang, Qiu-Ying Zhao, Jia-Hui Jiang, Biyu Shen, Yong Tang, Guang-Yin Xu","doi":"10.1016/j.neuron.2025.04.019","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.04.019","url":null,"abstract":"Chronic visceral pain (CVP) often accompanies emotional disorders. However, the lack of suitable animal models has hindered research into their underlying molecular and neural circuitry mechanisms. Early-life stress is a key factor in developing both visceral hypersensitivity and emotional disorders, yet its pathological mechanisms are not well understood. This study showed that adult offspring of prenatal maternal stress (PMS)-exposed mice exhibited visceral hypersensitivity and anxiety-like behaviors. Glutamatergic neurons in the anterior paraventricular thalamus (aPVT) responded to visceral pain, while those in the posterior PVT (pPVT) were more responsive to anxiety. The aPVT-basolateral amygdala (BLA) and pPVT-central amygdala (CeA) circuits regulated CVP and anxiety, respectively. Notably, increased Cacna1e expression in aPVT enhanced both visceral pain and anxiety, while Grin2a upregulation in pPVT facilitated only anxiety. These findings highlight the distinct roles of aPVTGlu-BLAGlu-CeAGABA and pPVTGlu-CeAGABA circuits, providing insights for therapeutic approaches in CVP and anxiety comorbidity.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974688","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

Common DISC1 Polymorphisms Disrupt Wnt/GSK3β Signaling and Brain Development. 常见DISC1多态性破坏Wnt/GSK3β信号传导和大脑发育

IF 14.7 1区医学

Neuron Pub Date : 2025-05-02 DOI: 10.1016/j.neuron.2025.04.021

Karun K Singh, Gianluca De Rienzo, Laurel Drane, Yingwei Mao, Zachary Flood, Jon Madison, Manuel Ferreira, Sarah Bergen, Cillian King, Pamela Sklar, Hazel Sive, Li-Huei Tsai

引用次数: 0

Lipid metabolism alterations in peripheral neuropathies. 周围神经病变的脂质代谢改变。

IF 14.7 1区医学

Neuron Pub Date : 2025-04-29 DOI: 10.1016/j.neuron.2025.04.006

Alessio Silva, Robert Prior, Maurizio D'Antonio, Johannes V Swinnen, Ludo Van Den Bosch

引用次数: 0

Nonneuronal contributions to synaptic function. 非神经元对突触功能的贡献。

IF 14.7 1区医学

Neuron Pub Date : 2025-04-25 DOI: 10.1016/j.neuron.2025.04.004

Ritchy Hodebourg, Michael D Scofield, Peter W Kalivas, Brittany N Kuhn

引用次数: 0

Metabolic reprogramming through histone lactylation in microglia and macrophages recruits CD8⁺ T lymphocytes and aggravates spinal cord injury. 通过小胶质细胞和巨噬细胞组蛋白乳酸化的代谢重编程募集CD8+ T淋巴细胞并加重脊髓损伤。

IF 14.7 1区医学

Neuron Pub Date : 2025-04-24 DOI: 10.1016/j.neuron.2025.04.003

Xuhui Ge, Yufeng Zhu, Junjun Xiong, Yao Gu, Xiaokun Wang, Wu Ye, Haofan Wang, Yu Gao, Weihua Cai, Xuhui Zhou, Wei Liu

{"title":"Metabolic reprogramming through histone lactylation in microglia and macrophages recruits CD8+ T lymphocytes and aggravates spinal cord injury.","authors":"Xuhui Ge, Yufeng Zhu, Junjun Xiong, Yao Gu, Xiaokun Wang, Wu Ye, Haofan Wang, Yu Gao, Weihua Cai, Xuhui Zhou, Wei Liu","doi":"10.1016/j.neuron.2025.04.003","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.04.003","url":null,"abstract":"Crosstalk between the central nervous system (CNS) and the immune system has recently gained increased attention; however, the interaction between innate and adaptive immunity after CNS injury remains unclear. Here, using single-cell RNA sequencing, we identified accumulation of CD8+ T lymphocytes in the cerebrospinal fluid of patients with spinal cord injury (SCI) and in spinal cords of injured mice, thus indicating poor neurological function. Furthermore, through genetic or pharmacologic interruption strategies, we found that CXCL16 chemokines derived from injury-activated microglia and macrophages (IAMs) recruited CXCR6+CD8+ T cells and further contributed to neuronal loss after SCI. Mechanistically, glycolytic reprogramming in IAMs enhanced histone-lactylation-mediated Cxcl16 transcription, whereas suppressing glycolysis through Pkm2 deletion partially reversed this effect. Notably, a pharmacologic intervention targeting the CXCL16-CXCR6 axis with Rutin promoted locomotor restoration after SCI. Our study highlights the crucial role of glycolytically reprogrammed IAM-derived CXCL16 chemokines in modulating a maladaptive innate/adaptive immune axis and reveals several potential therapeutic strategies.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007041","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

Chimeric brain models: Unlocking insights into human neural development, aging, diseases, and cell therapies. 嵌合脑模型：揭示人类神经发育，衰老，疾病和细胞治疗的见解。

IF 14.7 1区医学

Neuron Pub Date : 2025-04-22 DOI: 10.1016/j.neuron.2025.03.036

Ava V Papetti, Mengmeng Jin, Ziyuan Ma, Alessandro C Stillitano, Peng Jiang

引用次数: 0

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