Shwathy Ramesan, Joel Mason, Sandeep S. Kumar, Molly E. V. Swanson, Denis Korneev, Samuel A. Mills, Yasith Mathangasinghe, Aaron Andres, Lijun Loh, Tyra D. Fraser, Katherine N. Lewis, François-Xavier E. Beau, Stephanie Chua, Natasha Kapoor-Kaushik, Lewis J. Williams, Miran Mrkela, Bradley J. Turner, Georg Ramm, Matthew V. Rutar, Heejung Shim, David G. Gonsalvez, Samantha K. Barton
{"title":"A human-induced pluripotent stem cell-derived spheroid model to investigate myelin injury and repair","authors":"Shwathy Ramesan, Joel Mason, Sandeep S. Kumar, Molly E. V. Swanson, Denis Korneev, Samuel A. Mills, Yasith Mathangasinghe, Aaron Andres, Lijun Loh, Tyra D. Fraser, Katherine N. Lewis, François-Xavier E. Beau, Stephanie Chua, Natasha Kapoor-Kaushik, Lewis J. Williams, Miran Mrkela, Bradley J. Turner, Georg Ramm, Matthew V. Rutar, Heejung Shim, David G. Gonsalvez, Samantha K. Barton","doi":"10.1038/s41593-026-02457-z","DOIUrl":"https://doi.org/10.1038/s41593-026-02457-z","url":null,"abstract":"There are no currently approved therapies that promote new myelin formation after myelin damage, which can, in part, be attributed to a lack of reliable systems that can reproducibly model these processes. Here we engineered a human iPSC-derived spheroid model enriched with mature, myelinating oligodendrocytes and functionally reactive microglia. This model enables the study of human central nervous system remyelination after a demyelinating insult by recapitulating processes of myelin damage and repair. These include myelin fragmentation, microglial reactivity and phagocytosis of myelin debris, oligodendrocyte generation and differentiation, and axonal ensheathment with newly formed myelin. We show that newly generated oligodendrocytes contribute to remyelination, and use ultrastructural quantification to demonstrate that remyelinated axons are ensheathed by thinner myelin after injury. Altogether, we provide a model to interrogate otherwise inaccessible aspects of human myelin biology relevant to multiple sclerosis, providing mechanistic insights into disease pathways and a platform for drug screening.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"37 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087637","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}
Melissa Franch, Elizabeth A. Mickiewicz, James L. Belanger, Brad Joiner, Kalman A. Katlowitz, Hanlin Zhu, Ana G. Chavez, Assia Chericoni, Alica M. Goldman, Vaishnav Krishnan, Atul Maheshwari, Danika L. Paulo, Eleonora Bartoli, Suzanne Kemmer, Steven T. Piantadosi, Nicole R. Provenza, Jay A. Hennig, Sameer A. Sheth, Benjamin Y. Hayden
{"title":"A population code for semantics in human hippocampus","authors":"Melissa Franch, Elizabeth A. Mickiewicz, James L. Belanger, Brad Joiner, Kalman A. Katlowitz, Hanlin Zhu, Ana G. Chavez, Assia Chericoni, Alica M. Goldman, Vaishnav Krishnan, Atul Maheshwari, Danika L. Paulo, Eleonora Bartoli, Suzanne Kemmer, Steven T. Piantadosi, Nicole R. Provenza, Jay A. Hennig, Sameer A. Sheth, Benjamin Y. Hayden","doi":"10.1038/s41593-026-02436-4","DOIUrl":"https://doi.org/10.1038/s41593-026-02436-4","url":null,"abstract":"Motivated by the successes of large language models (LLMs), we hypothesized that semantic information in the brain may be expressed in distributed patterns of neural activity. We recorded responses of hippocampal neurons while individuals listened to narrative speech. Here, using an encoding model approach, we find robust encoding of semantics, even after controlling for phonemics and grammar. Individual words had complex selectivities that included multiple words in multiple semantic categories. Similar to embedding vectors in LLMs, distance between neural population responses correlated with semantic distance. For semantically similar words, even contextual embedders showed an inverse correlation between semantic and neural distances; we attribute this pattern to the noise-mitigating benefits of contrastive coding. Finally, neural population activity aligned most closely with GPT-2 embeddings, and variation in response patterns correlated with LLM-derived polysemy measures, indicating that semantic encoding is largely contextualized. Ultimately, these results provide a neurocomputational account for understanding how hippocampal neurons encode word meaning during language listening.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"45 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087638","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}
Giulia Faini, Matthieu Tuffery, Amna Saleem, Lixia Zhang, Felix Du, Guillaume Le Bourdelles, Karine Duroure, Eric R. Schreiter, Dimitrii Tanese, Valentina Emiliani, Filippo Del Bene, Minoru Koyama
{"title":"CLOK: a chemigenetic multicolor labeling system to visualize neuronal birthdate and circuit integration","authors":"Giulia Faini, Matthieu Tuffery, Amna Saleem, Lixia Zhang, Felix Du, Guillaume Le Bourdelles, Karine Duroure, Eric R. Schreiter, Dimitrii Tanese, Valentina Emiliani, Filippo Del Bene, Minoru Koyama","doi":"10.1038/s41593-026-02423-9","DOIUrl":"https://doi.org/10.1038/s41593-026-02423-9","url":null,"abstract":"Understanding how neurons integrate into developing circuits and contribute to functional activity is essential for decoding brain development and plasticity. However, current methods to study neuronal integration often suffer from low throughput, limited spatiotemporal resolution or invasive procedures. To overcome these challenges, here we present CLOK, an in vivo birthdate-labeling strategy based on HaloTag technology and its broad palette of fluorescent ligands. We show that CLOK enables precise color-coding of neurons and their subcellular structures by birthdate and allows tracking of functional maturation of newborn neurons in the developing zebrafish visual and motor systems, revealing distinct maturation trajectories of early- and late-born neurons. We further demonstrate the versatility of this approach by coupling it to optical tools enabling age-specific multicolor calcium and voltage imaging, as well as optogenetic manipulation. Altogether, CLOK provides a powerful and flexible tool for optical interrogation of neuronal circuit maturation in a growing and behaving vertebrate.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"18 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087622","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 neural architecture for imagined and overt speech motor dynamics.","authors":"Zehao Zhao, Zhenjie Wang, Yan Liu, Youkun Qian, Yuan Yin, Xiaowei Gao, Binke Yuan, Shelley Xiuli Tong, Xing Tian, Gao Chen, Yuanning Li, Junfeng Lu, Jinsong Wu","doi":"10.1038/s41593-026-02456-0","DOIUrl":"https://doi.org/10.1038/s41593-026-02456-0","url":null,"abstract":"<p><p>Mental imagery is a hallmark of human cognition, yet its neural mechanisms remain poorly understood. Speech imagery (the internal simulation of speech without overt articulation) has been proposed to partially share substrates with speech production, but its spatiotemporal dynamics remain controversial. Here, we leveraged high-resolution electrocorticography to investigate shared and modality-specific coding of articulatory kinematic trajectories during speech imagery and articulation. Linear modeling revealed robust articulatory kinematic trajectories encoding in frontoparietal cortex across modalities. Supramodal populations across middle premotor, subcentral and postcentral-supramarginal regions exhibited spatiotemporal stability during integrative planning. In contrast, modality-specific populations for speech imagery and articulation were somatotopically interleaved in primary sensorimotor cortex, revealing a distinct spatiotemporal organization. We further developed a generalized decoding framework that achieved high prediction accuracy for speech imagery (median 80.4%; chance 16.7%), comparable to speech articulation (78.3%). These findings uncover a somato-cognitive organization linking supramodal planning with modality-specific representations, informing imagery-based brain-computer interfaces.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081646","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}
Andrea I Luppi, Lynn Uhrig, Jordy Tasserie, Golia Shafiei, Antoine Légaré, Kanako Muta, Junichi Hata, Hideyuki Okano, Daniel Golkowski, Andreas Ranft, Rudiger Ilg, Denis Jordan, Silvia Gini, Zhen-Qi Liu, Yohan Yee, Pablo Castro, Camilo M Signorelli, Rodrigo Cofre, Alain Destexhe, David K Menon, Emmanuel A Stamatakis, Patrick Desrosiers, Paul De Koninck, Christopher W Connor, Alessandro Gozzi, Ben D Fulcher, Bechir Jarraya, Bratislav Misic
{"title":"Comprehensive profiling of brain dynamics during anesthesia across phylogeny.","authors":"Andrea I Luppi, Lynn Uhrig, Jordy Tasserie, Golia Shafiei, Antoine Légaré, Kanako Muta, Junichi Hata, Hideyuki Okano, Daniel Golkowski, Andreas Ranft, Rudiger Ilg, Denis Jordan, Silvia Gini, Zhen-Qi Liu, Yohan Yee, Pablo Castro, Camilo M Signorelli, Rodrigo Cofre, Alain Destexhe, David K Menon, Emmanuel A Stamatakis, Patrick Desrosiers, Paul De Koninck, Christopher W Connor, Alessandro Gozzi, Ben D Fulcher, Bechir Jarraya, Bratislav Misic","doi":"10.1038/s41593-026-02460-4","DOIUrl":"10.1038/s41593-026-02460-4","url":null,"abstract":"<p><p>The behavioral effects of anesthetics are highly conserved across species, hinting at shared and fundamental underlying mechanisms. Here we compile a dataset of multiscale neural activity during wakefulness and anesthesia, encompassing human, macaque, marmoset, mouse, zebrafish and nematode. Applying massive feature extraction, we characterize local neural dynamics across >6,000 time-series features. This reveals a conserved dynamical profile of anesthesia across species, characterized by shorter intrinsic timescales of neural activity and dampened inter-regional synchrony. Deep-brain stimulation of the macaque centromedian thalamus reverses this profile and restores behavioral responsiveness. This conserved dynamical phenotype covaries with conserved transcriptional profiles of excitatory and inhibitory neurotransmission. Biophysical modeling provides a potential mechanistic link between the macroscale dynamical phenotype of anesthesia and microscale effects of key molecular targets on the timescales of synaptic excitation and inhibition. These analyses reveal a shared neural endpoint of anesthesia: across species and scales, anesthetics induce spatiotemporal isolation of local neural activity.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081651","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":"Conserved neural dynamics of anesthesia and the oblivion of species.","authors":"George A Mashour, Zirui Huang","doi":"10.1038/s41593-026-02399-6","DOIUrl":"https://doi.org/10.1038/s41593-026-02399-6","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081725","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}
Kimberly L. Ray, Marietjie Botes, Melanie Collier, Alden Yi, Steven Hershman, Thaís Monteiro, Mariana Genuino, Jean-Baptiste Poline, Damian Eke, Ricardo Chavarriaga, Amadi Ogonda Ihunwo, Fernanda Tovar Moll, Thomas E. Nichols, Franco Pestilli
{"title":"Reconciling global collaboration and data sovereignty in neuroscience","authors":"Kimberly L. Ray, Marietjie Botes, Melanie Collier, Alden Yi, Steven Hershman, Thaís Monteiro, Mariana Genuino, Jean-Baptiste Poline, Damian Eke, Ricardo Chavarriaga, Amadi Ogonda Ihunwo, Fernanda Tovar Moll, Thomas E. Nichols, Franco Pestilli","doi":"10.1038/s41593-026-02468-w","DOIUrl":"10.1038/s41593-026-02468-w","url":null,"abstract":"As artificial intelligence (AI) elevates the economic and strategic value of data, governments are intensifying efforts to regulate the collection, use and cross-border transfer of personal information. Data are increasingly treated as national assets, subject to legal, economic and geopolitical controls. These shifts are reshaping scientific research, particularly in neuroscience and brain health, where progress depends on access to large, diverse and internationally distributed datasets. In parallel, advances in neuroimaging, neurotechnology and computational modeling are enabling population-scale neuroscience and the generation of AI-ready brain datasets. These developments further increase the strategic importance of neural data, amplifying both their scientific value and their governance complexity. The convergence of these trends exposes a fundamental tension between the need for an open science culture and data sovereignty. Without coordinated responses, these dynamics risk limiting representation, slowing innovation and reinforcing global inequities in brain health research. Here we argue that neuroscience requires an international data governance coordinating body capable of aligning research and regulatory priorities. In addition to outlining the distinct challenges posed by neural data, we propose strategies to support secure, equitable and sustainable global collaboration, as well as practical governance instruments to enable coordinated implementation across jurisdictions. Tension exists between the need for an open science culture and data sovereignty in global brain research. Ray et al. propose practical mechanisms for secure and equitable international collaboration.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"29 10","pages":"2397-2407"},"PeriodicalIF":20.3,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040199","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}
Nana Matoba,Jessica C. McAfee,Oleh Krupa,Alvaro A. Beltran,Jessica L. Bell,Brandon D. Le,Jordan M. Valone,Hyunggyu Min,Gregory E. Crawford,Jesse R. Raab,Hyejung Won,Jason L. Stein
{"title":"Massively parallel assessment of gene regulatory activity at human cortical-structure-associated variants","authors":"Nana Matoba,Jessica C. McAfee,Oleh Krupa,Alvaro A. Beltran,Jessica L. Bell,Brandon D. Le,Jordan M. Valone,Hyunggyu Min,Gregory E. Crawford,Jesse R. Raab,Hyejung Won,Jason L. Stein","doi":"10.1038/s41593-026-02454-2","DOIUrl":"https://doi.org/10.1038/s41593-026-02454-2","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"36 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149021161","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}
Zhiqing Cai, Zhimin Zhang, Yuxin Wang, Shencai Liu, Jiarong Leng, Yun Chu, Jihang Liu, Yingying Fang, Bochong Chen, Wenquan Liang, Hong Wang, Lu Zhang, Weiguo Zou, Fan Yang, Qiancheng Song, Di Lu, Xiaochun Bai
{"title":"Tibial bone compression promotes recovery after brain injury through osteocyte PIEZO1","authors":"Zhiqing Cai, Zhimin Zhang, Yuxin Wang, Shencai Liu, Jiarong Leng, Yun Chu, Jihang Liu, Yingying Fang, Bochong Chen, Wenquan Liang, Hong Wang, Lu Zhang, Weiguo Zou, Fan Yang, Qiancheng Song, Di Lu, Xiaochun Bai","doi":"10.1038/s41593-026-02422-w","DOIUrl":"https://doi.org/10.1038/s41593-026-02422-w","url":null,"abstract":"Traumatic brain injury (TBI) accelerates bone healing and induces heterotopic ossification, raising the question of whether an injured brain benefits from bone. Here we reveal that dynamic compressive tibial axial loading (DCTAL), a model of tibial bone compression, increased survival and promoted motor and cognitive recovery after stroke and TBI in mice, as well as in pig TBI models. DCTAL reduced neuron loss, attenuated chronic inflammation and astrogliosis and stimulated neuronal regeneration after TBI. Deletion of the mechanosensory channel Piezo1 in osteocytes reversed these benefits, while serum from DCTAL mice recapitulated them. Osteocytes transduced mechanical signals to directly secrete factors such as IL-1R2, APOL11a and HSP70, while indirectly increasing serum levels of BDNF, PF4 and dopamine. These factors synergistically protected against TBI. Altogether, we establish a bone–brain axis in which bone endocrine function can be modulated by mechanical forces to enhance brain repair after injury.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"17 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149010475","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}
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