Neuron最新文献

{"title":"Divergent opioid-mediated suppression of inhibition between hippocampus and neocortex across species and development.","authors":"Adam P Caccavano, Anna Vlachos, Nadiya McLean, Sarah Kimmel, June Hoan Kim, Geoffrey Vargish, Vivek Mahadevan, Lauren Hewitt, Anthony M Rossi, Ilona Spineux, Sherry Jingjing Wu, Elisabetta Furlanis, Min Dai, Brenda Leyva Garcia, Yating Wang, Ramesh Chittajallu, Edra London, Xiaoqing Yuan, Steven Hunt, Daniel Abebe, Mark A G Eldridge, Alex C Cummins, Brendan E Hines, Anya Plotnikova, Arya Mohanty, Bruno B Averbeck, Kareem A Zaghloul, Jordane Dimidschstein, Gord Fishell, Kenneth A Pelkey, Chris J McBain","doi":"10.1016/j.neuron.2025.03.005","DOIUrl":"10.1016/j.neuron.2025.03.005","url":null,"abstract":"<p><p>Within adult rodent hippocampus (HPC), opioids suppress inhibitory parvalbumin-expressing interneurons (PV-INs), disinhibiting local microcircuits. However, it is unknown whether this disinhibitory motif is conserved across cortical regions, species, or development. We observed that PV-IN-mediated inhibition is robustly suppressed by opioids in HPC proper but not primary neocortex in mice and non-human primates, with spontaneous inhibitory tone in resected human tissue also following a consistent dichotomy. This hippocampal disinhibitory motif is established in early development when PV-INs and opioids regulate early population activity. Morphine pretreatment partially occludes this acute opioid-mediated suppression, with implications for the effects of opioids on hippocampal network activity important for learning and memory. Our findings demonstrate that PV-INs exhibit divergent opioid sensitivity across brain regions, which is remarkably conserved over evolution, and highlight the underappreciated role of opioids acting through immature PV-INs in shaping hippocampal development.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730946","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}

{"title":"Key-value memory in the brain.","authors":"Samuel J Gershman, Ila Fiete, Kazuki Irie","doi":"10.1016/j.neuron.2025.02.029","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.02.029","url":null,"abstract":"<p><p>Classical models of memory in psychology and neuroscience rely on similarity-based retrieval of stored patterns, where similarity is a function of retrieval cues and the stored patterns. Although parsimonious, these models do not allow distinct representations for storage and retrieval, despite their distinct computational demands. Key-value memory systems, in contrast, distinguish representations used for storage (values) and those used for retrieval (keys). This allows key-value memory systems to optimize simultaneously for fidelity in storage and discriminability in retrieval. We review the computational foundations of key-value memory, its role in modern machine-learning systems, related ideas from psychology and neuroscience, applications to a number of empirical puzzles, and possible biological implementations.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730949","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}

{"title":"Vascular motion in the dorsal root ganglion sensed by Piezo2 in sensory neurons triggers episodic neuropathic pain.","authors":"Wenrui Xie, Debora Denardin Lückemeyer, Katherine A Qualls, Arthur Silveira Prudente, Temugin Berta, Mingxia Gu, Judith A Strong, Xinzhong Dong, Jun-Ming Zhang","doi":"10.1016/j.neuron.2025.03.006","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.03.006","url":null,"abstract":"<p><p>Spontaneous pain, characterized by episodic shooting or stabbing sensations, is a major complaint among neuropathic pain patients, yet its mechanisms remain poorly understood. Recent research indicates a connection between this pain condition and \"clustered firing,\" wherein adjacent sensory neurons fire simultaneously. This study presents evidence that the triggers of spontaneous pain and clustered firing are the dynamic movements of small blood vessels within the nerve-injured sensory ganglion, along with increased blood vessel density/angiogenesis and increased number of pericytes around blood vessels. Pharmacologically or mechanically evoked myogenic vascular responses increase both spontaneous pain and clustered firing in a mouse model of neuropathic pain. The mechanoreceptor Piezo2 in sensory neurons plays a critical role in detecting blood vessel movements. An anti-VEGF monoclonal antibody that inhibits angiogenesis effectively blocks spontaneous pain and clustered firing. These findings suggest targeting Piezo2, angiogenesis, or abnormal vascular dynamics as potential therapeutic strategies for neuropathic spontaneous pain.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743202","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}

{"title":"Single-cell spatial transcriptomic atlas of the whole mouse brain.","authors":"Lei Han, Zhen Liu, Zehua Jing, Yuxuan Liu, Yujie Peng, Huizhong Chang, Junjie Lei, Kexin Wang, Yuanfang Xu, Wei Liu, Zihan Wu, Qian Li, Xiaoxue Shi, Mingyuan Zheng, He Wang, Juan Deng, Yanqing Zhong, Hailin Pan, Junkai Lin, Ruiyi Zhang, Yu Chen, Jinhua Wu, Mingrui Xu, Biyu Ren, Mengnan Cheng, Qian Yu, Xinxiang Song, Yanbing Lu, Yuanchun Tang, Nini Yuan, Suhong Sun, Yingjie An, Wenqun Ding, Xing Sun, Yanrong Wei, Shuzhen Zhang, Yannong Dou, Yun Zhao, Luyao Han, Qianhua Zhu, Junfeng Xu, Shiwen Wang, Dan Wang, Yinqi Bai, Yikai Liang, Yuan Liu, Mengni Chen, Chun Xie, Binshi Bo, Mei Li, Xinyan Zhang, Wang Ting, Zhenhua Chen, Jiao Fang, Shuting Li, Yujia Jiang, Xing Tan, Guolong Zuo, Yue Xie, Huanhuan Li, Quyuan Tao, Yan Li, Jianfeng Liu, Yuyang Liu, Mingkun Hao, Jingjing Wang, Huiying Wen, Jiabing Liu, Yizhen Yan, Hui Zhang, Yifan Sheng, Shui Yu, Xiaoyan Liao, Xuyin Jiang, Guangling Wang, Huanlin Liu, Congcong Wang, Ning Feng, Xin Liu, Kailong Ma, Xiangjie Xu, Tianyue Han, Huateng Cao, Huiwen Zheng, Yadong Chen, Haorong Lu, Zixian Yu, Jinsong Zhang, Bo Wang, Zhifeng Wang, Qing Xie, Shanshan Pan, Chuanyu Liu, Chan Xu, Luman Cui, Yuxiang Li, Shiping Liu, Sha Liao, Ao Chen, Qing-Feng Wu, Jian Wang, Zhiyong Liu, Yidi Sun, Jan Mulder, Huanming Yang, Xiaofei Wang, Chao Li, Jianhua Yao, Xun Xu, Longqi Liu, Zhiming Shen, Wu Wei, Yan-Gang Sun","doi":"10.1016/j.neuron.2025.02.015","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.02.015","url":null,"abstract":"<p><p>A comprehensive atlas of genes, cell types, and their spatial distribution across a whole mammalian brain is fundamental for understanding the function of the brain. Here, using single-nucleus RNA sequencing (snRNA-seq) and Stereo-seq techniques, we generated a mouse brain atlas with spatial information for 308 cell clusters at single-cell resolution, involving over 4 million cells, as well as for 29,655 genes. We have identified cell clusters exhibiting preference for cortical subregions and explored their associations with brain-related diseases. Additionally, we pinpointed 155 genes with distinct regional expression patterns within the brainstem and unveiled 513 long non-coding RNAs showing region-enriched expression in the adult brain. Parcellation of brain regions based on spatial transcriptomic information revealed fine structure for several brain areas. Furthermore, we have uncovered 411 transcription factor regulons showing distinct spatiotemporal dynamics during neurodevelopment. Thus, we have constructed a single-cell-resolution spatial transcriptomic atlas of the mouse brain with genome-wide coverage.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710904","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}

{"title":"A pontine center in descending pain control.","authors":"Tianming Li, Wenjie Zhou, Jin Ke, Matthew Chen, Zhen Wang, Lauren Hayashi, Xiaojing Su, Wenbin Jia, Wenxi Huang, Chien-Sheng Wang, Kapsa Bengyella, Yang Yang, Rafael Hernandez, Yan Zhang, Xinglei Song, Tianle Xu, Tianwen Huang, Yuanyuan Liu","doi":"10.1016/j.neuron.2025.02.028","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.02.028","url":null,"abstract":"<p><p>Pain sensation changes according to expectation, context, and mood, illustrating how top-down circuits affect somatosensory processing. Here, we used an intersectional strategy to identify anatomical and molecular-spatial features of supraspinal descending neurons activated by distinct noxious stimulation. This approach captured known descending pain pathways as well as spinal projecting neurons that are anatomically mapped to Barrington's nucleus in the dorsal pontine tegmentum. We determined that this population of neurons expresses corticotropin-releasing hormone in Barrington's nucleus (Bar^Crh) and exhibits time-locked firing in response to noxious stimulation. Chemogenetic activation of Bar^Crh neurons attenuated nocifensive responses as well as tactile neuropathic pain, while silencing these neurons resulted in thermal hyperalgesia and mechanical allodynia. Mechanistically, we demonstrated that pain-related input from the ventrolateral periaqueductal gray recruits Bar^Crh neurons, reduces ascending nociceptive transmission, and preferentially activates spinal dynorphin neurons to mediate analgesia. Our data expose a pontine inhibitory descending pathway that powerfully controls nocifensive sensory input to the brain.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710900","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}

{"title":"Parental origin of transgene modulates amyloid-β plaque burden in the 5xFAD mouse model of Alzheimer's disease.","authors":"Andrew Octavian Sasmita, Erinne Cherisse Ong, Taisiia Nazarenko, Shuying Mao, Lina Komarek, Maik Thalmann, Veronika Hantakova, Lena Spieth, Stefan A Berghoff, Helena J Barr, Maximilian Hingerl, Friederike Börensen, Johannes Hirrlinger, Mikael Simons, Beth Stevens, Constanze Depp, Klaus-Armin Nave","doi":"10.1016/j.neuron.2024.12.025","DOIUrl":"10.1016/j.neuron.2024.12.025","url":null,"abstract":"<p><p>In Alzheimer's disease (AD) research, the 5xFAD mouse model is commonly used as a heterozygote crossed with other genetic models to study AD pathology. We investigated whether the parental origin of the 5xFAD transgene affects plaque deposition. Using quantitative light-sheet microscopy, we found that paternal inheritance of the transgene led to a 2-fold higher plaque burden compared with maternal inheritance, a finding consistent across multiple 5xFAD colonies. This effect was not due to gestation in or rearing by 5xFAD females. Immunoblotting suggested that transgenic inheritance modulates transgenic protein expression, potentially due to genomic imprinting of the Thy1.2 promoter. Surprisingly, fewer than 20% of 5xFAD studies report breeding schemes, suggesting that this factor might confound previous findings. Our data highlight a significant determinant of plaque burden in 5xFAD mice and underscore the importance of reporting the parental origin of the transgene to improve scientific rigor and reproducibility in AD research.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"838-846.e4"},"PeriodicalIF":14.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009079","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}

{"title":"Glioma-induced alterations in excitatory neurons are reversed by mTOR inhibition.","authors":"Alexander R Goldberg, Athanassios Dovas, Daniela Torres, Brianna Pereira, Ashwin Viswanathan, Sohani Das Sharma, Angeliki Mela, Edward M Merricks, Cristina Megino-Luque, Julie J McInvale, Markel Olabarria, Leila Abrishami Shokooh, Hanzhi T Zhao, Cady Chen, Corina Kotidis, Peter Calvaresi, Matei A Banu, Aida Razavilar, Tejaswi D Sudhakar, Ankita Saxena, Cole Chokran, Nelson Humala, Aayushi Mahajan, Weihao Xu, Jordan B Metz, Eric A Bushong, Daniela Boassa, Mark H Ellisman, Elizabeth M C Hillman, Gunnar Hargus, Jose Javier Bravo-Cordero, Guy M McKhann, Brian J A Gill, Steven S Rosenfeld, Catherine A Schevon, Jeffrey N Bruce, Peter A Sims, Darcy S Peterka, Peter Canoll","doi":"10.1016/j.neuron.2024.12.026","DOIUrl":"10.1016/j.neuron.2024.12.026","url":null,"abstract":"<p><p>Gliomas are aggressive neoplasms that diffusely infiltrate the brain and cause neurological symptoms, including cognitive deficits and seizures. Increased mTOR signaling has been implicated in glioma-induced neuronal hyperexcitability, but the molecular and functional consequences have not been identified. Here, we show three types of changes in tumor-associated neurons: (1) downregulation of transcripts encoding excitatory and inhibitory postsynaptic proteins and dendritic spine development and upregulation of cytoskeletal transcripts via neuron-specific profiling of ribosome-bound mRNA, (2) marked decreases in dendritic spine density via light and electron microscopy, and (3) progressive functional alterations leading to neuronal hyperexcitability via in vivo calcium imaging. A single acute dose of AZD8055, a combined mTORC1/2 inhibitor, reversed these tumor-induced changes. These findings reveal mTOR-driven pathological plasticity in neurons at the infiltrative margin of glioma and suggest new strategies for treating glioma-associated neurological symptoms.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"858-875.e10"},"PeriodicalIF":14.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009077","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}

{"title":"Amygdalo-cortical dialogue underlies memory enhancement by emotional association.","authors":"Yoshihito Saito, Yuma Osako, Maya Odagawa, Yasuhiro Oisi, Chie Matsubara, Shigeki Kato, Kazuto Kobayashi, Mitsuhiro Morita, Joshua P Johansen, Masanori Murayama","doi":"10.1016/j.neuron.2025.01.001","DOIUrl":"10.1016/j.neuron.2025.01.001","url":null,"abstract":"<p><p>Emotional arousal plays a critical role in determining what is remembered from experiences. It is hypothesized that activation of the amygdala by emotional stimuli enhances memory consolidation in its downstream brain regions. However, the physiological basis of the inter-regional interaction and its functions remain unclear. Here, by adding emotional information to a perceptual recognition task that relied on a frontal-sensory cortical circuit in mice, we demonstrated that the amygdala not only associates emotional information with perceptual information but also enhances perceptual memory retention via amygdalo-frontal cortical projections. Furthermore, emotional association increased reactivation of coordinated activity across the amygdalo-cortical circuit during non-rapid eye movement (NREM) sleep but not during rapid eye movement (REM) sleep. Notably, this increased reactivation was associated with amygdala high-frequency oscillations. Silencing of amygdalo-cortical inputs during NREM sleep selectively disrupted perceptual memory enhancement. Our findings indicate that inter-regional reactivation triggered by the amygdala during NREM sleep underlies emotion-induced perceptual memory enhancement.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"931-948.e7"},"PeriodicalIF":14.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066980","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}

{"title":"Divergent sex-specific pannexin-1 mechanisms in microglia and T cells underlie neuropathic pain.","authors":"Churmy Y Fan, Brendan B McAllister, Sierra Stokes-Heck, Erika K Harding, Aliny Pereira de Vasconcelos, Laura K Mah, Lucas V Lima, Nynke J van den Hoogen, Sarah F Rosen, Boram Ham, Zizhen Zhang, Hongrui Liu, Franz J Zemp, Regula Burkhard, Markus B Geuking, Douglas J Mahoney, Gerald W Zamponi, Jeffrey S Mogil, Shalina S Ousman, Tuan Trang","doi":"10.1016/j.neuron.2025.01.005","DOIUrl":"10.1016/j.neuron.2025.01.005","url":null,"abstract":"<p><p>Chronic pain is a leading cause of disability, affecting more women than men. Different immune cells contribute to this sexual divergence, but the mechanisms, especially in females, are not well defined. We show that pannexin-1 (Panx1) channels on microglia and T cells differentially cause mechanical allodynia, a debilitating symptom of neuropathic pain. In male rodents, Panx1 drives vascular endothelial growth factor-A (VEGF-A) release from microglia. Cell-specific knockdown of microglial Panx1 or pharmacological blockade of the VEGF receptor attenuated allodynia in nerve-injured males. In females, nerve injury increased spinal CD8⁺ T cells and leptin levels. Leptin release from female-derived CD8⁺ T cells was Panx1 dependent, and intrathecal leptin-neutralizing antibody injection sex-specifically reversed allodynia. Adoptive transfer of female-derived CD8⁺ T cells caused robust allodynia, which was prevented by a leptin-neutralizing antibody or leptin small interfering RNA (siRNA) knockdown. Panx1-targeted approaches may alleviate neuropathic pain in both sexes, while T cell- and leptin-directed treatments could have sex-dependent benefits for women.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"896-911.e9"},"PeriodicalIF":14.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075274","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}

{"title":"Sweet dreams are made of this: How emotions influence sleep-dependent consolidation of perceptual memories.","authors":"Azul Silva, Gabrielle Girardeau","doi":"10.1016/j.neuron.2025.02.024","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.02.024","url":null,"abstract":"<p><p>Emotions strongly modulate long-term memory retention, yet the underlying mechanisms remain unclear. Using causal and correlational approaches, Saito et al.¹ found that basolateral amygdala inputs to the M2-S1 cortical loop enhance the sleep-dependent consolidation of a perceptual-emotional associative memory.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":"113 6","pages":"803-805"},"PeriodicalIF":14.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670277","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}