IF 15 1区医学

Neuron Pub Date : 2025-08-20 Epub Date: 2025-06-06 DOI: 10.1016/j.neuron.2025.05.016

Giulia Demenego, Sara Mancinelli, Antonella Borreca, Rosalba Olga Proce, Vanessa Aragona, Matteo Miotto, Marco Cremonesi, Laura Zucchelli, Irene Corradini, Eugene Kim, Katarina Ilic, Edoardo Fraviga, Luca Pellegrino, Raffaele Badolato, Roberto Rusconi, Davide Pozzi, Marinos Kallikourdis, Diana Cash, Michela Matteoli, Simona Lodato

{"title":"Neurodevelopmental origins of structural and psychomotor defects in CXCR4-linked primary immunodeficiency.","authors":"Giulia Demenego, Sara Mancinelli, Antonella Borreca, Rosalba Olga Proce, Vanessa Aragona, Matteo Miotto, Marco Cremonesi, Laura Zucchelli, Irene Corradini, Eugene Kim, Katarina Ilic, Edoardo Fraviga, Luca Pellegrino, Raffaele Badolato, Roberto Rusconi, Davide Pozzi, Marinos Kallikourdis, Diana Cash, Michela Matteoli, Simona Lodato","doi":"10.1016/j.neuron.2025.05.016","DOIUrl":"10.1016/j.neuron.2025.05.016","url":null,"abstract":"Inborn errors of immunity (IEI), as congenital chronic disorders, are often associated with neurobehavioral symptoms, traditionally considered secondary to patient burden. Their origin, however, has yet to be addressed. Here, we found that IEI-associated genes are expressed in neural lineages during human brain development, and in the absence of immunological challenges, IEI mutations directly impair neurodevelopmental trajectories, leading to psychomotor defects. Warts hypogammaglobulinemia immunodeficiency myelokathexis (WHIM) mice-bearing a mutation causing Cxcr4 hyperactivation-show developmental foliation defects of the cerebellum correlating with sensorimotor and affective dysfunctions, which recapitulate the alterations described in patients. WHIM cerebella single-cell profiling revealed major transcriptional deregulation in granule cell progenitors, whose aberrant proliferation and migration induce foliation and circuit defects. AMD3100 intracerebroventricular injection rescues both morphological and behavioral defects, demonstrating their brain-specific and Cxcr4-dependent origin. Collectively, our findings highlight the relevance of neurodevelopmental implications underlying psychomotor IEI manifestations, broadening our understanding of these conditions beyond immune dysfunctions.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"2636-2655.e9"},"PeriodicalIF":15.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12416883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248974","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

Molecular and spatial analysis of ganglion cells on retinal flatmounts identifies perivascular neurons resilient to glaucoma 视网膜平支架上神经节细胞的分子和空间分析鉴定了对青光眼有弹性的血管周围神经元

IF 16.2 1区医学

Neuron Pub Date : 2025-08-20 DOI: 10.1016/j.neuron.2025.07.025

Kushal Nimkar, Nicole Y. Tsai, Mengya Zhao, Yujuan Yi, Matthew R. Lum, Tavita R. Garrett, Yixiao Wang, Kenichi Toma, Franklin Caval-Holme, Nikhil Reddy, Aliza T. Ehrlich, Arnold R. Kriegstein, Michael Tri H. Do, Yang Hu, Benjamin Sivyer, Karthik Shekhar, Xin Duan

{"title":"Molecular and spatial analysis of ganglion cells on retinal flatmounts identifies perivascular neurons resilient to glaucoma","authors":"Kushal Nimkar, Nicole Y. Tsai, Mengya Zhao, Yujuan Yi, Matthew R. Lum, Tavita R. Garrett, Yixiao Wang, Kenichi Toma, Franklin Caval-Holme, Nikhil Reddy, Aliza T. Ehrlich, Arnold R. Kriegstein, Michael Tri H. Do, Yang Hu, Benjamin Sivyer, Karthik Shekhar, Xin Duan","doi":"10.1016/j.neuron.2025.07.025","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.07.025","url":null,"abstract":"Recent transcriptomic studies have categorized mouse retinal ganglion cells (RGCs) into 45 types; however, little is known about their spatial distributions on the two-dimensional retinal surface and how their local microenvironments impact their functions. Here, we optimized a workflow combining imaging-based spatial transcriptomics (multiplexed-error robust fluorescent <ce:italic>in situ</ce:italic> hybridization [MERFISH]) and immunostaining on retinal flatmounts. We computationally registered the somata distributions of all RGCs and found that 34/45 molecularly defined types exhibited non-uniform distributions. We analyzed local neighborhoods for each cell and identified seven RGC types enriched in the perivascular niche, including direction-selective RGC (DSGC) and intrinsically photosensitive RGC (ipRGC) types. We further examined an experimental glaucoma model and found that surviving RGCs are enriched in the perivascular niche. Perivascular DSGCs and M1 ipRGCs were especially resilient, suggesting that proximity to vasculatures confers mTOR-independent, cell-extrinsic neuroprotection. Together, our work provides a comprehensive spatial atlas of RGC types and links their microenvironment to differential vulnerability in neurodegeneration.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":"7 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900509","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

Immunoregulator multitasking in neurons is not just a WHIM. 神经元中的免疫调节多任务处理不仅仅是一时兴起。

IF 15 1区医学

Neuron Pub Date : 2025-08-20 DOI: 10.1016/j.neuron.2025.07.027

Philip M Murphy

引用次数: 0

Disentangling frontal-striatal contributions to exploration. 解开额纹状体对勘探的贡献。

IF 15 1区医学

Neuron Pub Date : 2025-08-20 DOI: 10.1016/j.neuron.2025.07.022

Matthew Ainsworth, Mark J Buckley

引用次数: 0

Epigenetic signature of depression susceptibility in cortical astrocytes. 皮层星形胶质细胞抑郁易感性的表观遗传学特征。

IF 15 1区医学

Neuron Pub Date : 2025-08-20 DOI: 10.1016/j.neuron.2025.07.019

Yihui Cui

引用次数: 0

Microglia regulate neuronal activity via structural remodeling of astrocytes. 小胶质细胞通过星形胶质细胞的结构重塑调节神经元活动。

IF 15 1区医学

Neuron Pub Date : 2025-08-13 DOI: 10.1016/j.neuron.2025.07.024

Ning Gu, Olena Makashova, Celeste Laporte, Chris Qilongyue Chen, Banruo Li, Pierre-Marie Chevillard, Graham Lean, Jieyi Yang, Calvin Wong, Jonathan Fan, Behrang Sharif, Susana Puche Saud, Misha Hubacek, Katrina Y Choe, Margaret M McCarthy, Arkady Khoutorsky, Charles W Bourque, Masha Prager-Khoutorsky

{"title":"Microglia regulate neuronal activity via structural remodeling of astrocytes.","authors":"Ning Gu, Olena Makashova, Celeste Laporte, Chris Qilongyue Chen, Banruo Li, Pierre-Marie Chevillard, Graham Lean, Jieyi Yang, Calvin Wong, Jonathan Fan, Behrang Sharif, Susana Puche Saud, Misha Hubacek, Katrina Y Choe, Margaret M McCarthy, Arkady Khoutorsky, Charles W Bourque, Masha Prager-Khoutorsky","doi":"10.1016/j.neuron.2025.07.024","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.07.024","url":null,"abstract":"Neuron-glia interactions play a central role in regulating synaptic transmission and neuronal excitability. The structural plasticity of astrocytes is associated with numerous physiological and pathological conditions; however, the mechanism underlying this process remains unknown. To examine the basis for structural astrocyte plasticity, we used the classic example of the loss of astrocytic processes that takes place in the rat hypothalamic magnocellular system during chronic high-salt intake. We discovered that a high-salt diet triggers a local accumulation of reactive microglia around vasopressin-secreting neurons but not in other brain areas. Microglia phagocytose astrocytic processes, reducing astrocytic coverage of vasopressin neurons. The pruning of astrocytic processes impairs synaptic glutamate clearance, enabling activation of extrasynaptic glutamate NMDA receptors and increasing the activity of vasopressin neurons. Inhibiting microglia-mediated astrocyte pruning attenuates the increased neuronal activity and vasopressin-dependent hypertensive phenotype of rats fed a high-salt diet. Thus, microglia orchestrate neuron-glia interactions and regulate neuronal activity through astrocyte pruning.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963020","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

Optimized deep brain stimulation for anterior cingulate cortex inhibition produces antidepressant-like effects in mice. 对前扣带皮层抑制的优化脑深部刺激在小鼠中产生抗抑郁样效果。

IF 15 1区医学

Neuron Pub Date : 2025-08-08 DOI: 10.1016/j.neuron.2025.07.018

Zhengwei Yuan, Haonan Yang, Peng Wang, Xiaoning Hou, Ke Xu, Yu Zhou, Ruicheng Dai, Yuan Gao, Xinwei Gao, Qingchun Guo, Yulong Li, Jianning Zhang, Zhiqi Mao, Minmin Luo

{"title":"Optimized deep brain stimulation for anterior cingulate cortex inhibition produces antidepressant-like effects in mice.","authors":"Zhengwei Yuan, Haonan Yang, Peng Wang, Xiaoning Hou, Ke Xu, Yu Zhou, Ruicheng Dai, Yuan Gao, Xinwei Gao, Qingchun Guo, Yulong Li, Jianning Zhang, Zhiqi Mao, Minmin Luo","doi":"10.1016/j.neuron.2025.07.018","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.07.018","url":null,"abstract":"Deep brain stimulation (DBS) emerges as a promising intervention for psychiatric disorders, including major depressive disorder (MDD). The optimal stimulation parameters and the neural circuit mechanisms of DBS remain areas of active investigation. This study combines DBS with fiber photometry to monitor neuronal activity in the mouse anterior cingulate cortex (ACC), a key region implicated in depression. By systematically optimizing DBS parameters-including waveform, pulse width, and frequency-we identified configurations that robustly inhibited or activated ACC activity. Inhibitory DBS elicited rapid-onset and long-lasting antidepressant-like behaviors in mouse models of depression, while excitatory DBS induced anhedonia in otherwise healthy mice. Using an inverse activity marker, we mapped the downstream effects of ACC DBS, revealing broad inhibition across emotion- and mood-regulation networks. These findings establish a principled framework for DBS parameter optimization and identify ACC-targeted inhibition as a potential therapeutic strategy for MDD.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862361","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

Coordination of distinct sources of excitatory inputs enhances motion selectivity in the mouse visual thalamus. 不同兴奋性输入源的协调增强了小鼠视丘脑的运动选择性。

IF 15 1区医学

Neuron Pub Date : 2025-08-07 DOI: 10.1016/j.neuron.2025.07.015

Yue Fei, Michelle Y Luh, Ashley Ontiri, Dawood Ghauri, Wenxin Hu, Liang Liang

{"title":"Coordination of distinct sources of excitatory inputs enhances motion selectivity in the mouse visual thalamus.","authors":"Yue Fei, Michelle Y Luh, Ashley Ontiri, Dawood Ghauri, Wenxin Hu, Liang Liang","doi":"10.1016/j.neuron.2025.07.015","DOIUrl":"10.1016/j.neuron.2025.07.015","url":null,"abstract":"Multiple sources innervate the visual thalamus to influence image-forming vision prior to the cortex, yet coordination between non-retinal and retinal inputs in shaping thalamic visual selectivity remains unclear. Using dual-color two-photon calcium imaging in the thalamus of awake mice, we observed a higher fraction of direction-selective boutons among input from superior colliculus neurons than from retinal ganglion cells, both providing strong converging excitatory input to thalamic neurons. Collicular and retinal axons exhibit retinotopic organization with similar precision. At a fine scale of ∼10 μm, collicular boutons often shared feature preferences with nearby retinal boutons. Inhibiting collicular input significantly suppressed visual responses in thalamic shell neurons and specifically reduced selectivity in neurons preferring motion along the temporal direction or horizontal axis. These findings suggest that the thalamus is not merely a relay but selectively integrates inputs from multiple regions to build stimulus selectivity and shape the information transmitted to the cortex.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855839","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

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

IF 15 1区医学

Neuron Pub Date : 2025-08-06 Epub Date: 2025-04-30 DOI: 10.1016/j.neuron.2025.04.004

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

引用次数: 0

Multimodal analyses reveal genes driving electrophysiological maturation of neurons in the primate prefrontal cortex. 多模态分析揭示了驱动灵长类前额皮质神经元电生理成熟的基因。

IF 15 1区医学

Neuron Pub Date : 2025-08-06 Epub Date: 2025-05-20 DOI: 10.1016/j.neuron.2025.04.025

Yu Gao, Qiping Dong, Kalpana Hanthanan Arachchilage, Ryan D Risgaard, Moosa Syed, Jie Sheng, Danielle K Schmidt, Ting Jin, Shuang Liu, Soraya O Sandoval, Sara Knaack, Magnus T Eckholm, Rachel J Chen, Yu Guo, Dan Doherty, Ian Glass, Jon E Levine, Daifeng Wang, Qiang Chang, Xinyu Zhao, Andre M M Sousa

{"title":"Multimodal analyses reveal genes driving electrophysiological maturation of neurons in the primate prefrontal cortex.","authors":"Yu Gao, Qiping Dong, Kalpana Hanthanan Arachchilage, Ryan D Risgaard, Moosa Syed, Jie Sheng, Danielle K Schmidt, Ting Jin, Shuang Liu, Soraya O Sandoval, Sara Knaack, Magnus T Eckholm, Rachel J Chen, Yu Guo, Dan Doherty, Ian Glass, Jon E Levine, Daifeng Wang, Qiang Chang, Xinyu Zhao, Andre M M Sousa","doi":"10.1016/j.neuron.2025.04.025","DOIUrl":"10.1016/j.neuron.2025.04.025","url":null,"abstract":"The prefrontal cortex (PFC) is critical for myriad high-cognitive functions and is associated with several neuropsychiatric disorders. Here, using Patch-seq and single-nucleus multiomic analyses, we identified genes and regulatory networks governing the maturation of distinct neuronal populations in the PFC of rhesus macaque. We discovered that specific electrophysiological properties exhibited distinct maturational kinetics and identified key genes underlying these properties. We unveiled that RAPGEF4 is important for the maturation of resting membrane potential and inward sodium current in both macaque and human. We demonstrated that knockdown of CHD8, a high-confidence autism risk gene, in human and macaque organotypic slices led to impaired maturation, via downregulation of key genes, including RAPGEF4. Restoring the expression of RAPGEF4 rescued the proper electrophysiological maturation of CHD8-deficient neurons. Our study revealed regulators of neuronal maturation during a critical period of PFC development in primates and implicated such regulators in molecular processes underlying autism.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"2490-2507.e16"},"PeriodicalIF":15.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12331439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120323","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

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