Nature neuroscience最新文献

Gene programs driving cortical neuron specifications

IF 25 1区医学

Nature neuroscience Pub Date : 2025-04-21 DOI: 10.1038/s41593-025-01934-1

Zhisong He, Barbara Treutlein

引用次数: 0

Integrated analysis of molecular atlases unveils modules driving developmental cell subtype specification in the human cortex

IF 25 1区医学

Nature neuroscience Pub Date : 2025-04-21 DOI: 10.1038/s41593-025-01933-2

Patricia R. Nano, Elisa Fazzari, Daria Azizad, Antoni Martija, Claudia V. Nguyen, Sean Wang, Vanna Giang, Ryan L. Kan, Juyoun Yoo, Brittney Wick, Maximilian Haeussler, Aparna Bhaduri

{"title":"Integrated analysis of molecular atlases unveils modules driving developmental cell subtype specification in the human cortex","authors":"Patricia R. Nano, Elisa Fazzari, Daria Azizad, Antoni Martija, Claudia V. Nguyen, Sean Wang, Vanna Giang, Ryan L. Kan, Juyoun Yoo, Brittney Wick, Maximilian Haeussler, Aparna Bhaduri","doi":"10.1038/s41593-025-01933-2","DOIUrl":"https://doi.org/10.1038/s41593-025-01933-2","url":null,"abstract":"Human brain development requires generating diverse cell types, a process explored by single-cell transcriptomics. Through parallel meta-analyses of the human cortex in development (seven datasets) and adulthood (16 datasets), we generated over 500 gene co-expression networks that can describe mechanisms of cortical development, centering on peak stages of neurogenesis. These meta-modules show dynamic cell subtype specificities throughout cortical development, with several developmental meta-modules displaying spatiotemporal expression patterns that allude to potential roles in cell fate specification. We validated the expression of these modules in primary human cortical tissues. These include meta-module 20, a module elevated in FEZF2+ deep layer neurons that includes TSHZ3, a transcription factor associated with neurodevelopmental disorders. Human cortical chimeroid experiments validated that both FEZF2 and TSHZ3 are required to drive module 20 activity and deep layer neuron specification but through distinct modalities. These studies demonstrate how meta-atlases can engender further mechanistic analyses of cortical fate specification.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"30 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853194","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

IF 25 1区医学

Nature neuroscience Pub Date : 2025-04-21 DOI: 10.1038/s41593-025-01943-0

Łukasz J. Sznajder, Mahreen Khan, Adam Ciesiołka, Mariam Tadross, Curtis A. Nutter, Katarzyna Taylor, Christopher E. Pearson, Mark H. Lewis, Rochelle M. Hines, Maurice S. Swanson, Krzysztof Sobczak, Ryan K. C. Yuen

{"title":"Autism-related traits in myotonic dystrophy type 1 model mice are due to MBNL sequestration and RNA mis-splicing of autism-risk genes","authors":"Łukasz J. Sznajder, Mahreen Khan, Adam Ciesiołka, Mariam Tadross, Curtis A. Nutter, Katarzyna Taylor, Christopher E. Pearson, Mark H. Lewis, Rochelle M. Hines, Maurice S. Swanson, Krzysztof Sobczak, Ryan K. C. Yuen","doi":"10.1038/s41593-025-01943-0","DOIUrl":"https://doi.org/10.1038/s41593-025-01943-0","url":null,"abstract":"Genome-wide enrichment of gene-specific tandem repeat expansions has been linked to autism spectrum disorder. One such mutation is the CTG tandem repeat expansion in the 3′ untranslated region of the DMPK gene, which is known to cause myotonic muscular dystrophy type 1. Although there is a clear clinical association between autism and myotonic dystrophy, the molecular basis for this connection remains unknown. Here, we report that sequestration of MBNL splicing factors by mutant DMPK RNAs with expanded CUG repeats alters the RNA splicing patterns of autism-risk genes during brain development, particularly a class of autism-relevant microexons. We demonstrate that both DMPK-CTG expansion and Mbnl null mouse models recapitulate autism-relevant mis-splicing profiles, along with social behavioral deficits and altered responses to novelty. These findings support our model that myotonic dystrophy-associated autism arises from developmental mis-splicing of autism-risk genes.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"34 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853195","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

Dynamics of glia and neurons regulate homeostatic rest, sleep and feeding behavior in Drosophila

IF 25 1区医学

Nature neuroscience Pub Date : 2025-04-21 DOI: 10.1038/s41593-025-01942-1

Andres Flores-Valle, Ivan Vishniakou, Johannes D. Seelig

引用次数: 0

Functionally distinct GABAergic amacrine cell types regulate spatiotemporal encoding in the mouse retina

IF 25 1区医学

Nature neuroscience Pub Date : 2025-04-15 DOI: 10.1038/s41593-025-01935-0

Akihiro Matsumoto, Jacqueline Morris, Loren L. Looger, Keisuke Yonehara

{"title":"Functionally distinct GABAergic amacrine cell types regulate spatiotemporal encoding in the mouse retina","authors":"Akihiro Matsumoto, Jacqueline Morris, Loren L. Looger, Keisuke Yonehara","doi":"10.1038/s41593-025-01935-0","DOIUrl":"https://doi.org/10.1038/s41593-025-01935-0","url":null,"abstract":"GABA (γ-aminobutyric acid) is the primary inhibitory neurotransmitter in the mammalian central nervous system. GABAergic neuronal types play important roles in neural processing and the etiology of neurological disorders; however, there is no comprehensive understanding of their functional diversity. Here we perform two-photon imaging of GABA release in the inner plexiform layer of male and female mice retinae (8–16 weeks old) using the GABA sensor iGABASnFR2. By applying varied light stimuli to isolated retinae, we reveal over 40 different GABA-releasing neuron types. Individual types show layer-specific visual encoding within inner plexiform layer sublayers. Synaptic input and output sites are aligned along specific retinal orientations. The combination of cell type-specific spatial structure and unique release kinetics enables inhibitory neurons to sculpt excitatory signals in response to a wide range of behaviorally relevant motion structures. Our findings emphasize the importance of functional diversity and intricate specialization of GABAergic neurons in the central nervous system.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"40 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831701","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

Spatially clustered neurons in the bat midbrain encode vocalization categories

IF 25 1区医学

Nature neuroscience Pub Date : 2025-04-14 DOI: 10.1038/s41593-025-01932-3

Jennifer Lawlor, Melville J. Wohlgemuth, Cynthia F. Moss, Kishore V. Kuchibhotla

{"title":"Spatially clustered neurons in the bat midbrain encode vocalization categories","authors":"Jennifer Lawlor, Melville J. Wohlgemuth, Cynthia F. Moss, Kishore V. Kuchibhotla","doi":"10.1038/s41593-025-01932-3","DOIUrl":"https://doi.org/10.1038/s41593-025-01932-3","url":null,"abstract":"Rapid categorization of vocalizations enables adaptive behavior across species. While categorical perception is thought to arise in the neocortex, humans and animals could benefit from a functional organization tailored to ethologically relevant sound processing earlier in the auditory pathway. Here we developed two-photon calcium imaging in the awake echolocating bat (Eptesicus fuscus) to study the representation of vocalizations in the inferior colliculus, which is as few as two synapses from the inner ear. Echolocating bats rely on frequency-sweep-based vocalizations for social communication and navigation. Auditory playback experiments demonstrated that individual neurons responded selectively to social or navigation calls, enabling robust population-level decoding across categories. When social calls were morphed into navigation calls in equidistant step-wise increments, individual neurons showed switch-like properties and population-level response patterns sharply transitioned at the category boundary. Strikingly, category-selective neurons formed spatial clusters, independent of tonotopy within the dorsal cortex of the inferior colliculus. These findings support a revised view of categorical processing in which specified channels for ethologically relevant sounds are spatially segregated early in the auditory hierarchy, enabling rapid subcortical organization into categorical primitives.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"183 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827147","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

Hippocampal output suppresses orbitofrontal cortex schema cell formation

IF 25 1区医学

Nature neuroscience Pub Date : 2025-04-14 DOI: 10.1038/s41593-025-01928-z

Wenhui Zong, Jingfeng Zhou, Matthew P. H. Gardner, Zhewei Zhang, Kauê Machado Costa, Geoffrey Schoenbaum

引用次数: 0

Single-cell genomics of the mouse olfactory cortex reveals contrasts with neocortex and ancestral signatures of cell type evolution

IF 25 1区医学

Nature neuroscience Pub Date : 2025-04-08 DOI: 10.1038/s41593-025-01924-3

Sara Zeppilli, Alonso O. Gurrola, Pinar Demetci, David H. Brann, Tuan M. Pham, Robin Attey, Noga Zilkha, Tali Kimchi, Sandeep R. Datta, Ritambhara Singh, Maria A. Tosches, Anton Crombach, Alexander Fleischmann

{"title":"Single-cell genomics of the mouse olfactory cortex reveals contrasts with neocortex and ancestral signatures of cell type evolution","authors":"Sara Zeppilli, Alonso O. Gurrola, Pinar Demetci, David H. Brann, Tuan M. Pham, Robin Attey, Noga Zilkha, Tali Kimchi, Sandeep R. Datta, Ritambhara Singh, Maria A. Tosches, Anton Crombach, Alexander Fleischmann","doi":"10.1038/s41593-025-01924-3","DOIUrl":"https://doi.org/10.1038/s41593-025-01924-3","url":null,"abstract":"Understanding the molecular logic of cortical cell-type diversity can illuminate cortical circuit function and evolution. Here, we performed single-nucleus transcriptome and chromatin accessibility analyses to compare neurons across three- to six-layered cortical areas of adult mice and across tetrapod species. We found that, in contrast to the six-layered neocortex, glutamatergic neurons of the three-layered mouse olfactory (piriform) cortex displayed continuous rather than discrete variation in transcriptomic profiles. Subsets of piriform and neocortical glutamatergic cells with conserved transcriptomic profiles were distinguished by distinct, area-specific epigenetic states. Furthermore, we identified a prominent population of immature neurons in piriform cortex and observed that, in contrast to the neocortex, piriform cortex exhibited divergence between glutamatergic cells in laboratory versus wild-derived mice. Finally, we showed that piriform neurons displayed greater transcriptomic similarity to cortical neurons of turtles, lizards and salamanders than to those of the neocortex. In summary, despite over 200 million years of coevolution alongside the neocortex, olfactory cortex neurons retain molecular signatures of ancestral cortical identity.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"74 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797824","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

Microglia heterogeneity, modeling and cell-state annotation in development and neurodegeneration

IF 25 1区医学

Nature neuroscience Pub Date : 2025-04-07 DOI: 10.1038/s41593-025-01931-4

Laura Fumagalli, Alma Nazlie Mohebiany, Jessie Premereur, Paula Polanco Miquel, Baukje Bijnens, Pieter Van de Walle, Nicola Fattorelli, Renzo Mancuso

引用次数: 0

Sugar-coating the BBB 糖衣炮弹

IF 21.2 1区医学

Nature neuroscience Pub Date : 2025-04-04 DOI: 10.1038/s41593-025-01939-w

Shari Wiseman

引用次数: 0