{"title":"Social rank modulates methamphetamine-seeking in dominant and subordinate male rodents via distinct dopaminergic pathways","authors":"Xiaofei Deng, Wei Xu, Yutong Liu, Haiyang Jing, Jiafeng Zhong, Kaige Sun, Ruiyi Zhou, Liang Xu, Xiaocong Wu, Baofang Zhang, Wanqi Chen, Shaolei Jiang, Gaowei Chen, Yingjie Zhu","doi":"10.1038/s41593-025-01951-0","DOIUrl":"https://doi.org/10.1038/s41593-025-01951-0","url":null,"abstract":"<p>Social status has a profound impact on mental health and propensity towards drug addiction. However, the neural mechanisms underlying the effects of social rank on drug-seeking behavior remain unclear. Here we found that dominant male rodents (based on the tube test) had denser mesocortical dopaminergic projections and were more resistant to methamphetamine (METH)-seeking, whereas subordinates had heightened dopaminergic function in the mesolimbic pathway and were more vulnerable to METH seeking. Optogenetic activation of the mesocortical dopaminergic pathway promoted winning and suppressed METH seeking in subordinates, whereas lesions of the mesocortical pathway increased METH seeking in dominants. Elevation of social rank with forced win training in subordinates led to remodeling of the dopaminergic system and prevented METH-seeking behavior. In females, however, both ranks were susceptible to METH seeking, with mesocorticolimbic pathways comparable to those in subordinate males. These results provide a framework for understanding the neural basis of the impact of social status on drug-seeking.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933508","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":"Widespread brain–body integration during changes of arousal","authors":"","doi":"10.1038/s41593-025-01946-x","DOIUrl":"https://doi.org/10.1038/s41593-025-01946-x","url":null,"abstract":"Widespread, slow fluctuations in brain blood flow detected via functional MRI and neural activity are integrated with systemic physiological dynamics across the body. We showed this brain–body integration associates with the arousal response orchestrated by the autonomic nervous system.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"20 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926959","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":"An energy blueprint of the human brain","authors":"Henrietta Howells","doi":"10.1038/s41593-025-01967-6","DOIUrl":"https://doi.org/10.1038/s41593-025-01967-6","url":null,"abstract":"<p>Functional neuroimaging enables measurement of brain organization and dynamics, but it only indirectly measures the subcellular bioenergetic processes that power brain activity. As such, there has been a gap between these large-scale imaging techniques and the microscopic scale of mitochondrial bioenergetics. In their study published in <i>Nature</i>, Mosharov and colleagues present a method to bridge this gap by creating a spatial map of mitochondrial diversity across the brain. They cut frozen human brain tissue into 3-mm cubes, comparable in size to MRI voxels, and then registered them to MNI space. They used advanced biochemical assays to profile mitochondrial distribution and function, which were then compared with standard brain-imaging data from different modalities. The findings revealed substantial heterogeneity in mitochondrial density and oxidative phosphorylation capacity between gray and white matter. The distribution of mitochondria is suggestive of a gradient that aligns with the phylogenetic development of the brain. This study offers insight into the energetic infrastructure that supports brain function, and it has the potential to inform research into healthy brain development and disease.</p><p><b>Original reference:</b> <i>Nature</i> https://doi.org/10.1038/s41586-025-08740-6 (2025)</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"117 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920805","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":"Neuron subtypes play the long game","authors":"Luis A. Mejia","doi":"10.1038/s41593-025-01968-5","DOIUrl":"https://doi.org/10.1038/s41593-025-01968-5","url":null,"abstract":"<p>Approaches to assigning neurons to specific subtypes in the mouse brain are commonly based on electrophysiological, morphological and transcriptomic properties. Connectomic analyses for subtype classification have typically been restricted to electron microscopy datasets, but the authors of a study in <i>Nature Methods</i> instead leverage high-throughput single-neuron reconstruction datasets to classify cells on the basis of potential connectivity. The authors compiled a database of over 20,000 single-neuron morphological reconstructions and used machine learning to assign topologically connected axonal and dendritic arbors. Potential connectivity was therefore obtained from the overlap of dendritic and axonal arbor spatial domains. Importantly, classification of cells based on connectivity, or c-types, outperformed classification based on morphology, or conventional m-types, and substantially contributed to classification performance jointly with m-types. Further subtyping was possible using spatially correlated connectivity and morphological features. Using c-type classification, the authors were able to showcase subtyping of thalamic and thalamocortical neurons. Potential connectivity subtyping is thus a promising method by which to classify individual neurons in the brain into types.</p><p><b>Original reference:</b> <i>Nat. Methods</i> https://doi.org/10.1038/s41592-025-02621-6 (2025)</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"7 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920772","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":"Stress and autophagy","authors":"Leonie Welberg","doi":"10.1038/s41593-025-01969-4","DOIUrl":"https://doi.org/10.1038/s41593-025-01969-4","url":null,"abstract":"<p>Stress disrupts homeostasis, and although various processes in the brain quickly restore equilibrium following acute stress, this is not the case during chronic stress, which can lead to depression. A paper published in <i>Nature</i> identifies autophagy as an important player in this phenomenon. The authors found that chronic stress in male mice downregulated autophagy in neurons in the lateral habenula (LHb) by increasing mTOR signaling. By contrast, acute stress increased autophagy in this area by increasing AMPK activation. Depression-like behavior in chronically stressed mice could be reversed or prevented by pharmacological activation of autophagy in the LHb. Various antidepressant drugs, including an mTOR inhibitor, required autophagy in this area to do their job. Autophagy mainly targeted postsynaptic glutamate receptors (GluRs) for degradation, and reduced autophagy — such as that in chronically stressed mice — was associated with excessive GluR expression and caused LHb neuron hyperactivity, impaired synaptic long-term depression, and depression-like behavior. Together, these findings show that autophagy is important for maintaining homeostasis in the LHb by counterbalancing the excessive GluRs upregulated by stress, and they suggest that restoring autophagy, possibly with an mTOR inhibitor, may be a promising target for antidepressant research.</p><p><b>Original reference:</b> <i>Nature</i> https://www.nature.com/articles/s41586-025-08807-4 (2025)</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"48 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920771","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}
Maheva Andriatsilavo, Carolina Barata, Eric Reifenstein, Alexandre Dumoulin, Tian Tao Griffin, Suchetana Bias Dutta, Esther T. Stoeckli, Max von Kleist, P. Robin Hiesinger, Bassem A. Hassan
{"title":"Sequential and independent probabilistic events regulate differential axon targeting during development in Drosophila melanogaster","authors":"Maheva Andriatsilavo, Carolina Barata, Eric Reifenstein, Alexandre Dumoulin, Tian Tao Griffin, Suchetana Bias Dutta, Esther T. Stoeckli, Max von Kleist, P. Robin Hiesinger, Bassem A. Hassan","doi":"10.1038/s41593-025-01937-y","DOIUrl":"https://doi.org/10.1038/s41593-025-01937-y","url":null,"abstract":"<p>Variation in brain wiring contributes to non-heritable behavioral individuality. How and when these individualized wiring patterns emerge and stabilize during development remains unexplored. In this study, we investigated the axon targeting dynamics of <i>Drosophila</i> visual projecting neurons called DCNs/LC14s, using four-dimensional live-imaging, mathematical modeling and experimental validation. We found that alternative axon targeting choices are driven by a sequence of two independent genetically encoded stochastic processes. Early Notch lateral inhibition segregates DCNs into Notch<sup>ON</sup> proximally targeting axons and Notch<sup>OFF</sup> axons that adopt a bi-potential transitory state. Subsequently, probabilistic accumulation of stable microtubules in a fraction of Notch<sup>OFF</sup> axons leads to distal target innervation, whereas the rest retract to adopt a Notch<sup>ON</sup> target choice. The sequential wiring decisions result in the stochastic selection of different numbers of distally targeting axons in each individual. In summary, this work provides a conceptual and mechanistic framework for the emergence of individually variable, yet robust, circuit diagrams during development.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"31 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915720","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}
Taylor Bolt, Shiyu Wang, Jason S. Nomi, Roni Setton, Benjamin P. Gold, Blaise deB.Frederick, B. T. Thomas Yeo, J. Jean Chen, Dante Picchioni, Jeff H. Duyn, R. Nathan Spreng, Shella D. Keilholz, Lucina Q. Uddin, Catie Chang
{"title":"Autonomic physiological coupling of the global fMRI signal","authors":"Taylor Bolt, Shiyu Wang, Jason S. Nomi, Roni Setton, Benjamin P. Gold, Blaise deB.Frederick, B. T. Thomas Yeo, J. Jean Chen, Dante Picchioni, Jeff H. Duyn, R. Nathan Spreng, Shella D. Keilholz, Lucina Q. Uddin, Catie Chang","doi":"10.1038/s41593-025-01945-y","DOIUrl":"https://doi.org/10.1038/s41593-025-01945-y","url":null,"abstract":"<p>The brain is closely attuned to visceral signals from the body’s internal environment, as evidenced by the numerous associations between neural, hemodynamic and peripheral physiological signals. Here we show that a major mode of these brain–body cofluctuations can be captured by a single spatiotemporal pattern. Across several independent samples, as well as single-echo and multi-echo functional magnetic resonance imaging (fMRI) data acquisition sequences, we identify widespread cofluctuations in the low-frequency range (0.01–0.1 Hz) between resting-state global fMRI signals, electroencephalogram (EEG) activity, and a host of peripheral autonomic signals spanning cardiovascular, pulmonary, exocrine and smooth muscle systems. The same brain–body cofluctuations observed at rest are elicited by cued deep breathing and intermittent sensory stimuli, as well as spontaneous phasic EEG events during sleep. Furthermore, we show that the spatial structure of global fMRI signals is maintained under experimental suppression of end-tidal carbon dioxide variations, suggesting that respiratory-driven fluctuations in arterial CO<sub>2</sub> accompanying arousal cannot fully explain the origin of these signals in the brain. These findings suggest that the global fMRI signal is a substantial component of the arousal response governed by the autonomic nervous system.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"47 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915713","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}
Andres Flores-Valle, Ivan Vishniakou, Johannes D. Seelig
{"title":"Author Correction: Dynamics of glia and neurons regulate homeostatic rest, sleep and feeding behavior in Drosophila","authors":"Andres Flores-Valle, Ivan Vishniakou, Johannes D. Seelig","doi":"10.1038/s41593-025-01984-5","DOIUrl":"https://doi.org/10.1038/s41593-025-01984-5","url":null,"abstract":"<p>Correction to: <i>Nature Neuroscience</i> https://doi.org/10.1038/s41593-025-01942-1, published online 21 April 2025.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"18 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909782","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}
Sara E. Zsadanyi, Elizabeth Addison, Suvarna Alladi, Shea J. Andrews, Keerthana BS, Giovanna Carello-Collar, Olga Dubljević, Alexander J. Ehrenberg, Francesca R. Farina, Lea T. Grinberg, Agustin Ibáñez, Adam Martersteck, Abebaw Nigussie, Emily J. Rogalski, Kaitlin Seibert, Elka Stefanova, Kristine Yaffe, Yared Z. Zewde, Eduardo R. Zimmer, Igor C. Fontana, Claire E. Sexton
{"title":"Democratizing dementia research through global online conferences","authors":"Sara E. Zsadanyi, Elizabeth Addison, Suvarna Alladi, Shea J. Andrews, Keerthana BS, Giovanna Carello-Collar, Olga Dubljević, Alexander J. Ehrenberg, Francesca R. Farina, Lea T. Grinberg, Agustin Ibáñez, Adam Martersteck, Abebaw Nigussie, Emily J. Rogalski, Kaitlin Seibert, Elka Stefanova, Kristine Yaffe, Yared Z. Zewde, Eduardo R. Zimmer, Igor C. Fontana, Claire E. Sexton","doi":"10.1038/s41593-025-01949-8","DOIUrl":"https://doi.org/10.1038/s41593-025-01949-8","url":null,"abstract":"Following the COVID-19 pandemic, a shift from traditional in-person conferences to virtual and hybrid formats was welcomed for its accessible, cost-effective approach to sharing scientific knowledge and connecting people. Here, we discuss an effective hybrid format that combines in-person and online elements to foster inclusivity by providing a flexible, cost-effective alternative to in-person meetings.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"95 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909958","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}
Cathy J. Price, Peter Zeidman, Martina F. Callaghan
{"title":"Eleanor Maguire (1970–2025)","authors":"Cathy J. Price, Peter Zeidman, Martina F. Callaghan","doi":"10.1038/s41593-025-01974-7","DOIUrl":"https://doi.org/10.1038/s41593-025-01974-7","url":null,"abstract":"Eleanor Maguire was a visionary cognitive neuroscientist whose research transformed our understanding of how the brain supports memory, navigation, and imagination.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"53 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143910501","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}