IF 15 1区医学

Neuron Pub Date : 2025-09-18 DOI: 10.1016/j.neuron.2025.08.022

Shilin Zhong, Xiaoting Zhang, Xinwei Gao, Zhongyu Li, Linling Huang, Qingchun Guo, Rong Gong, Jing Ren, Minmin Luo, Rui Lin

{"title":"Ultrabright chemical labeling enables rapid neural connectivity profiling in large tissue samples.","authors":"Shilin Zhong, Xiaoting Zhang, Xinwei Gao, Zhongyu Li, Linling Huang, Qingchun Guo, Rong Gong, Jing Ren, Minmin Luo, Rui Lin","doi":"10.1016/j.neuron.2025.08.022","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.08.022","url":null,"abstract":"Comprehensive mapping of neuronal connections across entire nervous systems remains a fundamental challenge in neuroscience. Here, we introduce labeling individual neurons with chemical dyes and controllable sparseness (LINCS), a technology that achieves rapid, ultrabright, and photostable labeling of specific cell types throughout the entire mouse brain and body. LINCS utilizes an engineered, solubility-enhanced biotin ligase for in vivo biotinylation, followed by rapid whole-mount staining with a high-affinity monovalent streptavidin. When integrated with tissue clearing and light-sheet microscopy, this system creates an efficient pipeline for profiling long-range neuronal projections across both the central and peripheral nervous systems. Furthermore, we developed an adeno-associated virus (AAV) strategy employing Cas9-mediated Cre knockout to achieve stable sparse labeling, permitting the precise morphological reconstruction of individual neurons at scale. The LINCS toolkit substantially lowers the barrier to large-scale connectivity mapping and will accelerate the anatomical and functional dissection of mammalian neural circuits.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092131","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

Unlocking the epigenome: Single-cell histone profiling in cortical development. 解锁表观基因组：皮质发育中的单细胞组蛋白谱。

IF 15 1区医学

Neuron Pub Date : 2025-09-17 DOI: 10.1016/j.neuron.2025.07.026

Yong-Qi Gao, Fides Zenk

引用次数: 0

Sleep and the recovery from stress. 睡眠和从压力中恢复。

IF 15 1区医学

Neuron Pub Date : 2025-09-17 Epub Date: 2025-05-22 DOI: 10.1016/j.neuron.2025.04.028

Xiao Yu, Mathieu Nollet, Nicholas P Franks, William Wisden

引用次数: 0

Variation in moment-to-moment brain state engagement follows a consistent trajectory during development. 在发展过程中，大脑每时每刻的状态变化遵循着一致的轨迹。

IF 15 1区医学

Neuron Pub Date : 2025-09-17 DOI: 10.1016/j.neuron.2025.08.020

Jean Ye, Link Tejavibulya, Wei Dai, Lora M Cope, Jillian E Hardee, Mary M Heitzeg, Sarah Lichenstein, Sarah W Yip, Tobias Banaschewski, Gareth J Baker, Arun L W Bokde, Rüdiger Brühl, Sylvane Desrivières, Herta Flor, Penny Gowland, Antoine Grigis, Andreas Heinz, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Eric Artiges, Frauke Nees, Dimitri Papadopoulos Orfanos, Luise Poustka, Sarah Hohmann, Nathalie Holz, Christian Baeuchl, Michael N Smolka, Nilakshi Vaidya, Henrik Walter, Robert Whelan, Gunter Schumann, Hugh Garavan, Bader Chaarani, Dylan G Gee, Arielle Baskin-Sommers, B J Casey, Dustin Scheinost

{"title":"Variation in moment-to-moment brain state engagement follows a consistent trajectory during development.","authors":"Jean Ye, Link Tejavibulya, Wei Dai, Lora M Cope, Jillian E Hardee, Mary M Heitzeg, Sarah Lichenstein, Sarah W Yip, Tobias Banaschewski, Gareth J Baker, Arun L W Bokde, Rüdiger Brühl, Sylvane Desrivières, Herta Flor, Penny Gowland, Antoine Grigis, Andreas Heinz, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Eric Artiges, Frauke Nees, Dimitri Papadopoulos Orfanos, Luise Poustka, Sarah Hohmann, Nathalie Holz, Christian Baeuchl, Michael N Smolka, Nilakshi Vaidya, Henrik Walter, Robert Whelan, Gunter Schumann, Hugh Garavan, Bader Chaarani, Dylan G Gee, Arielle Baskin-Sommers, B J Casey, Dustin Scheinost","doi":"10.1016/j.neuron.2025.08.020","DOIUrl":"10.1016/j.neuron.2025.08.020","url":null,"abstract":"Neural variability, or variation in brain signals, facilitates dynamic brain responses to ongoing demands. This flexibility is important during development from childhood to young adulthood, a period characterized by rapid changes in experience. However, little is known about how variability in moment-to-moment brain state engagement changes during development. Such investigations would require the continuous assessment of multiple brain states concurrently. Here, we leverage a new computational framework to characterize the state engagement variability (SEV) developmental trajectory. A consistent pattern of SEV changing with age is identified across cross-sectional and longitudinal datasets (N > 3,000). The SEV developmental trajectory stabilizes around mid-adolescence, with timing varying by sex and brain state. SEV successfully predicts executive function (EF) in youth from an independent dataset. Deviations in SEV development are further linked to worse EF. These converging findings suggest that SEV changes over development, allowing individuals to flexibly recruit various brain states to meet evolving needs.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12483157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086657","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 "five-star matrix" for patient-centric drug discovery and development in neuroscience. 神经科学中以患者为中心的药物发现和开发的“五星矩阵”。

IF 15 1区医学

Neuron Pub Date : 2025-09-17 Epub Date: 2025-09-04 DOI: 10.1016/j.neuron.2025.08.004

Axel Pähler, Eoin C O'Connor, Hayley Binch, Sherri Dudal, Luca C Gobbi, Thomas Lübbers, Andrés Olivares-Morales, Rosa María Rodríguez Sarmiento, Uwe Grether, Martin Stahl, Gennaro Pagano, Antonia F Stepan

{"title":"The \"five-star matrix\" for patient-centric drug discovery and development in neuroscience.","authors":"Axel Pähler, Eoin C O'Connor, Hayley Binch, Sherri Dudal, Luca C Gobbi, Thomas Lübbers, Andrés Olivares-Morales, Rosa María Rodríguez Sarmiento, Uwe Grether, Martin Stahl, Gennaro Pagano, Antonia F Stepan","doi":"10.1016/j.neuron.2025.08.004","DOIUrl":"10.1016/j.neuron.2025.08.004","url":null,"abstract":"Progress in understanding human biology has revealed potential therapeutic targets for brain disorders. Yet, the discovery of new neuroscience drugs is often hampered by the lack of precise translation tools and disease models, resulting in high preclinical and clinical failure rates. To improve success, robust translational foundations linking pharmacological targets to disease phenotypes are essential. The \"five-star matrix\" offers a comprehensive framework for translational drug discovery, consisting of five \"dimensions\" (biodistribution, target binding/occupancy, proximal effect, biological effect, and disease effect) and five \"systems\" (biochemical, cellular, ex vivo, preclinical, and clinical). By identifying translatable biomarkers across these dimensions and systems, researchers can test hypotheses from early target assessments to clinical studies. Although linking pathogenic processes to disease-relevant endpoints is challenging, applying the five-star matrix across neuroscience projects fosters collaboration to develop holistic, patient-centric strategies with clear deliverables toward clinical proof of concept. Case studies illustrate the rationale for the five-star matrix in creating a translational continuum from bench to bedside.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"2885-2909"},"PeriodicalIF":15.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006336","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

Maternal inheritance suppresses CAA and amyloid plaques in 5xFAD (Tg7031)/APOE4 mice. 母体遗传抑制5xFAD (Tg7031)/APOE4小鼠的CAA和淀粉样斑块。

IF 15 1区医学

Neuron Pub Date : 2025-09-17 DOI: 10.1016/j.neuron.2025.08.008

Fareeha Saadi, Ilia V Katritch, Samira Parhizkar, Brisa Lugo, Yoonho Cho, Jason D Ulrich, David M Holtzman

引用次数: 0

Representations of stimulus features in the ventral hippocampus. 腹侧海马体刺激特征的表征。

IF 15 1区医学

Neuron Pub Date : 2025-09-17 Epub Date: 2025-07-30 DOI: 10.1016/j.neuron.2025.06.007

Jeremy S Biane, Max A Ladow, Austin Fan, Hye Sun Choi, Lexi Zichen Zhou, Shazreh Hassan, Daniel L Apodaca-Montano, Andrew O Kwon, Joshua X Bratsch-Prince, Mazen A Kheirbek

{"title":"Representations of stimulus features in the ventral hippocampus.","authors":"Jeremy S Biane, Max A Ladow, Austin Fan, Hye Sun Choi, Lexi Zichen Zhou, Shazreh Hassan, Daniel L Apodaca-Montano, Andrew O Kwon, Joshua X Bratsch-Prince, Mazen A Kheirbek","doi":"10.1016/j.neuron.2025.06.007","DOIUrl":"10.1016/j.neuron.2025.06.007","url":null,"abstract":"Discriminating and categorizing the meaning of environmental stimuli and responding accordingly are essential for survival. The ventral hippocampus (vHPC) controls emotional and motivated behaviors in response to environmental cues and is hypothesized to do so in part by deciphering the positive or negative quality of these cues. Yet, what features of the environment are represented in the activity patterns of ventral CA1 (vCA1) neurons and whether the positive or negative meaning of stimuli is present at this stage remain unclear. Here, using two-photon calcium imaging across six experimental paradigms, we examined which features of salient stimuli are represented by vCA1 ensembles and found that identity, sensory features, and intensity-but not valence-are robustly encoded. These results offer a reappraisal of the vCA1 function, wherein information corresponding to individual stimulus features, and not their meaning, predominates. This organizational scheme may support flexible updating of stimulus value as internal states and environmental demands change.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"3015-3030.e6"},"PeriodicalIF":15.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760618","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

Negative results positive for understanding the neural representation of valence across the brain. 阴性结果对理解整个大脑中价的神经表征是阳性的。

IF 15 1区医学

Neuron Pub Date : 2025-09-17 DOI: 10.1016/j.neuron.2025.08.024

Sounak Mohanta, Kay M Tye

引用次数: 0

A unifying mechanism for presynaptic homeostatic plasticity at mammalian peripheral and central synapses. 哺乳动物外周和中枢突触突触前稳态可塑性的统一机制。

IF 15 1区医学

Neuron Pub Date : 2025-09-17 Epub Date: 2025-06-30 DOI: 10.1016/j.neuron.2025.05.030

Peter H Chipman, Unghwi Lee, Brian O Orr, Richard D Fetter, Graeme W Davis

{"title":"A unifying mechanism for presynaptic homeostatic plasticity at mammalian peripheral and central synapses.","authors":"Peter H Chipman, Unghwi Lee, Brian O Orr, Richard D Fetter, Graeme W Davis","doi":"10.1016/j.neuron.2025.05.030","DOIUrl":"10.1016/j.neuron.2025.05.030","url":null,"abstract":"Presynaptic homeostatic plasticity (PHP) is a potent form of adaptive plasticity that has been documented at synapses as diverse as the glutamatergic Drosophila neuromuscular junction (NMJ), cholinergic mammalian NMJ (including human), and glutamatergic synapses in the mammalian brain. We define secreted class III semaphorin as a unifying, trans-synaptic signal necessary for PHP at highly divergent synapses. Sema3a drives the rapid induction of PHP at the cholinergic mouse NMJ and synapses in the adult hippocampus (CA1), including cross-modal potentiation of inhibitory transmission. Three-dimensional electron microscopy (EM) reveals Sema3a-dependent active zone expansion, presynaptic stabilization, and the maintenance of synapse organization during PHP. Mechanistically, Sema3a promotes vesicle redistribution from a non-releasing to recycling and readily releasable vesicle pool. Finally, presynaptic-signal transduction is also commonly deployed, requiring activation of PlexinA4 and an integrin beta-1 (ITGB1) co-receptor. The widespread utilization of common PHP mechanisms emphasizes the translational potential of model organisms toward promoting neuronal resilience to combat brain disorders and disease.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"2945-2961.e6"},"PeriodicalIF":15.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12370254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144541602","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

Spontaneous movements and their relationship to neural activity fluctuate with latent engagement states. 自发运动及其与神经活动的关系随潜在接触状态而波动。

IF 15 1区医学

Neuron Pub Date : 2025-09-17 Epub Date: 2025-07-01 DOI: 10.1016/j.neuron.2025.06.001

Chaoqun Yin, Maxwell D Melin, Gabriel Rojas-Bowe, Xiaonan Richard Sun, João Couto, Steven Gluf, Alex Kostiuk, Simon Musall, Anne K Churchland

{"title":"Spontaneous movements and their relationship to neural activity fluctuate with latent engagement states.","authors":"Chaoqun Yin, Maxwell D Melin, Gabriel Rojas-Bowe, Xiaonan Richard Sun, João Couto, Steven Gluf, Alex Kostiuk, Simon Musall, Anne K Churchland","doi":"10.1016/j.neuron.2025.06.001","DOIUrl":"10.1016/j.neuron.2025.06.001","url":null,"abstract":"Switching between cognitive states is a natural tendency, even for trained experts. To test how cognitive states impact neural activity and behavior, we measured cortex-wide neural activity during decision-making in mice. During disengagement, neural activity was more variable across trials and could be better explained by a linear encoding model. This increase in explained variance during disengagement was associated with two changes: modestly stronger neural encoding of movements generally and an increase in task-independent movements specifically. Surprisingly, behavioral videos showed similar motion energy in both cognitive states. But while the overall amount of movements remained similar, movement alignment changed: as animals slipped into disengagement, their movements became less stereotyped. These idiosyncratic movements were a strong predictor of task performance and engagement. Taken together, our results suggest that the temporal structure of movement patterns constitutes an embodied signature of the cognitive state with a profound relationship to neural activity.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"3048-3063.e5"},"PeriodicalIF":15.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554039","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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