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AI beats neuroscientists’ predictions
IF 21.2 1区 医学
Nature neuroscience Pub Date : 2025-01-08 DOI: 10.1038/s41593-024-01860-8
Henrietta Howells
{"title":"AI beats neuroscientists’ predictions","authors":"Henrietta Howells","doi":"10.1038/s41593-024-01860-8","DOIUrl":"10.1038/s41593-024-01860-8","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 1","pages":"3-3"},"PeriodicalIF":21.2,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142937085","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
Context-dependent decision-making in the primate hippocampal–prefrontal circuit
IF 25 1区 医学
Nature neuroscience Pub Date : 2025-01-06 DOI: 10.1038/s41593-024-01839-5
Thomas W. Elston, Joni D. Wallis
{"title":"Context-dependent decision-making in the primate hippocampal–prefrontal circuit","authors":"Thomas W. Elston, Joni D. Wallis","doi":"10.1038/s41593-024-01839-5","DOIUrl":"https://doi.org/10.1038/s41593-024-01839-5","url":null,"abstract":"<p>What is good in one scenario may be bad in another. Despite the ubiquity of such contextual reasoning in everyday choice, how the brain flexibly uses different valuation schemes across contexts remains unknown. We addressed this question by monitoring neural activity from the hippocampus (HPC) and orbitofrontal cortex (OFC) of two monkeys performing a state-dependent choice task. We found that HPC neurons encoded state information as it became available and then, at the time of choice, relayed this information to the OFC via theta synchronization. During choice, the OFC represented value in a state-dependent manner; many OFC neurons uniquely coded for value in only one state but not the other. This suggests a functional dissociation whereby the HPC encodes contextual information that is broadcast to the OFC via theta synchronization to select a state-appropriate value subcircuit, thereby allowing for contextual reasoning in value-based choice.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"88 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929723","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
Multimodal transcriptomics reveal neurogenic aging trajectories and age-related regional inflammation in the dentate gyrus
IF 25 1区 医学
Nature neuroscience Pub Date : 2025-01-06 DOI: 10.1038/s41593-024-01848-4
Yicheng Wu, Vladyslav I. Korobeynyk, Margherita Zamboni, Felix Waern, John Darby Cole, Sarah Mundt, Melanie Greter, Jonas Frisén, Enric Llorens-Bobadilla, Sebastian Jessberger
{"title":"Multimodal transcriptomics reveal neurogenic aging trajectories and age-related regional inflammation in the dentate gyrus","authors":"Yicheng Wu, Vladyslav I. Korobeynyk, Margherita Zamboni, Felix Waern, John Darby Cole, Sarah Mundt, Melanie Greter, Jonas Frisén, Enric Llorens-Bobadilla, Sebastian Jessberger","doi":"10.1038/s41593-024-01848-4","DOIUrl":"https://doi.org/10.1038/s41593-024-01848-4","url":null,"abstract":"<p>The mammalian dentate gyrus (DG) is involved in certain forms of learning and memory, and DG dysfunction has been implicated in age-related diseases. Although neurogenic potential is maintained throughout life in the DG as neural stem cells (NSCs) continue to generate new neurons, neurogenesis decreases with advancing age, with implications for age-related cognitive decline and disease. In this study, we used single-cell RNA sequencing to characterize transcriptomic signatures of neurogenic cells and their surrounding DG niche, identifying molecular changes associated with neurogenic aging from the activation of quiescent NSCs to the maturation of fate-committed progeny. By integrating spatial transcriptomics data, we identified the regional invasion of inflammatory cells into the hippocampus with age and show here that early-onset neuroinflammation decreases neurogenic activity. Our data reveal the lifelong molecular dynamics of NSCs and their surrounding neurogenic DG niche with age and provide a powerful resource to understand age-related molecular alterations in the aging hippocampus.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"21 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929721","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
Aberrant splicing in Huntington’s disease accompanies disrupted TDP-43 activity and altered m6A RNA modification
IF 25 1区 医学
Nature neuroscience Pub Date : 2025-01-06 DOI: 10.1038/s41593-024-01850-w
Thai B. Nguyen, Ricardo Miramontes, Carlos Chillon-Marinas, Roy Maimon, Sonia Vazquez-Sanchez, Alice L. Lau, Nicolette R. McClure, Zhuoxing Wu, Keona Q. Wang, Whitney E. England, Monika Singha, Jennifer T. Stocksdale, Marie Heath, Ki-Hong Jang, Sunhee Jung, Karen Ling, Paymann Jafar-nejad, Jharrayne I. McKnight, Leanne N. Ho, Osama Al Dalahmah, Richard L. M. Faull, Joan S. Steffan, Jack C. Reidling, Cholsoon Jang, Gina Lee, Don W. Cleveland, Clotilde Lagier-Tourenne, Robert C. Spitale, Leslie M. Thompson
{"title":"Aberrant splicing in Huntington’s disease accompanies disrupted TDP-43 activity and altered m6A RNA modification","authors":"Thai B. Nguyen, Ricardo Miramontes, Carlos Chillon-Marinas, Roy Maimon, Sonia Vazquez-Sanchez, Alice L. Lau, Nicolette R. McClure, Zhuoxing Wu, Keona Q. Wang, Whitney E. England, Monika Singha, Jennifer T. Stocksdale, Marie Heath, Ki-Hong Jang, Sunhee Jung, Karen Ling, Paymann Jafar-nejad, Jharrayne I. McKnight, Leanne N. Ho, Osama Al Dalahmah, Richard L. M. Faull, Joan S. Steffan, Jack C. Reidling, Cholsoon Jang, Gina Lee, Don W. Cleveland, Clotilde Lagier-Tourenne, Robert C. Spitale, Leslie M. Thompson","doi":"10.1038/s41593-024-01850-w","DOIUrl":"https://doi.org/10.1038/s41593-024-01850-w","url":null,"abstract":"<p>Huntington’s disease (HD) is caused by a CAG repeat expansion in the <i>HTT</i> gene, leading to altered gene expression. However, the mechanisms leading to disrupted RNA processing in HD remain unclear. Here we identify TDP-43 and the N6-methyladenosine (m6A) writer protein METTL3 to be upstream regulators of exon skipping in multiple HD systems. Disrupted nuclear localization of TDP-43 and cytoplasmic accumulation of phosphorylated TDP-43 occurs in HD mouse and human brains, with TDP-43 also co-localizing with HTT nuclear aggregate-like bodies distinct from mutant HTT inclusions. The binding of TDP-43 onto RNAs encoding HD-associated differentially expressed and aberrantly spliced genes is decreased. Finally, m6A RNA modification is reduced on RNAs abnormally expressed in the striatum of HD R6/2 mouse brain, including at clustered sites adjacent to TDP-43 binding sites. Our evidence supports TDP-43 loss of function coupled with altered m6A modification as a mechanism underlying alternative splicing in HD.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"99 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929446","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
Typical development of synaptic and neuronal properties can proceed without microglia in the cortex and thalamus
IF 25 1区 医学
Nature neuroscience Pub Date : 2025-01-06 DOI: 10.1038/s41593-024-01833-x
Mary O’Keeffe, Sam A. Booker, Darren Walsh, Mosi Li, Chloe Henley, Laura Simões de Oliveira, Mingshan Liu, Xingran Wang, Maria Banqueri, Katherine Ridley, Kosala N. Dissanayake, Cristina Martinez-Gonzalez, Kirsty J. Craigie, Deepali Vasoya, Tom Leah, Xin He, David A. Hume, Ian Duguid, Matthew F. Nolan, Jing Qiu, David J. A. Wyllie, Owen R. Dando, Alfredo Gonzalez-Sulser, Jian Gan, Clare Pridans, Peter C. Kind, Giles E. Hardingham
{"title":"Typical development of synaptic and neuronal properties can proceed without microglia in the cortex and thalamus","authors":"Mary O’Keeffe, Sam A. Booker, Darren Walsh, Mosi Li, Chloe Henley, Laura Simões de Oliveira, Mingshan Liu, Xingran Wang, Maria Banqueri, Katherine Ridley, Kosala N. Dissanayake, Cristina Martinez-Gonzalez, Kirsty J. Craigie, Deepali Vasoya, Tom Leah, Xin He, David A. Hume, Ian Duguid, Matthew F. Nolan, Jing Qiu, David J. A. Wyllie, Owen R. Dando, Alfredo Gonzalez-Sulser, Jian Gan, Clare Pridans, Peter C. Kind, Giles E. Hardingham","doi":"10.1038/s41593-024-01833-x","DOIUrl":"https://doi.org/10.1038/s41593-024-01833-x","url":null,"abstract":"<p>Brain-resident macrophages, microglia, have been proposed to have an active role in synaptic refinement and maturation, influencing plasticity and circuit-level connectivity. Here we show that several neurodevelopmental processes previously attributed to microglia can proceed without them. Using a genetically modified mouse that lacks microglia (<i>Csf1r</i><sup>∆FIRE/∆FIRE</sup>), we find that intrinsic properties, synapse number and synaptic maturation are largely normal in the hippocampal CA1 region and somatosensory cortex at stages where microglia have been implicated. Seizure susceptibility and hippocampal-prefrontal cortex coherence in awake behaving animals, processes that are disrupted in mice deficient in microglia-enriched genes, are also normal. Similarly, eye-specific segregation of inputs into the lateral geniculate nucleus proceeds normally in the absence of microglia. Single-cell and single-nucleus transcriptomic analyses of neurons and astrocytes did not uncover any substantial perturbation caused by microglial absence. Thus, the brain possesses remarkable adaptability to execute developmental synaptic refinement, maturation and connectivity in the absence of microglia.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929726","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
Monocyte-derived macrophages act as reinforcements when microglia fall short in Alzheimer’s disease
IF 25 1区 医学
Nature neuroscience Pub Date : 2025-01-06 DOI: 10.1038/s41593-024-01847-5
Miguel A. Abellanas, Maitreyee Purnapatre, Chiara Burgaletto, Michal Schwartz
{"title":"Monocyte-derived macrophages act as reinforcements when microglia fall short in Alzheimer’s disease","authors":"Miguel A. Abellanas, Maitreyee Purnapatre, Chiara Burgaletto, Michal Schwartz","doi":"10.1038/s41593-024-01847-5","DOIUrl":"https://doi.org/10.1038/s41593-024-01847-5","url":null,"abstract":"<p>The central nervous system (CNS) is endowed with its own resident innate immune cells, the microglia. They constitute approximately 10% of the total cells within the CNS parenchyma and act as ‘sentinels’, sensing and mitigating any deviation from homeostasis. Nevertheless, under severe acute or chronic neurological injury or disease, microglia are unable to contain the damage, and the reparative activity of monocyte-derived macrophages (MDMs) is required. The failure of the microglia under such conditions could be an outcome of their prolonged exposure to hostile stimuli, leading to their exhaustion or senescence. Here, we describe the conditions under which the microglia fall short, focusing mainly on the context of Alzheimer’s disease, and shed light on the functions performed by MDMs. We discuss whether and how MDMs engage in cross-talk with the microglia, why their recruitment is often inadequate, and potential ways to augment their homing to the brain in a well-controlled manner.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"78 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929724","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
NOMPC ion channel hinge forms a gating spring that initiates mechanosensation
IF 25 1区 医学
Nature neuroscience Pub Date : 2025-01-06 DOI: 10.1038/s41593-024-01849-3
Philip Hehlert, Thomas Effertz, Ruo-Xu Gu, Björn Nadrowski, Bart R. H. Geurten, Dirk Beutner, Bert L. de Groot, Martin C. Göpfert
{"title":"NOMPC ion channel hinge forms a gating spring that initiates mechanosensation","authors":"Philip Hehlert, Thomas Effertz, Ruo-Xu Gu, Björn Nadrowski, Bart R. H. Geurten, Dirk Beutner, Bert L. de Groot, Martin C. Göpfert","doi":"10.1038/s41593-024-01849-3","DOIUrl":"https://doi.org/10.1038/s41593-024-01849-3","url":null,"abstract":"<p>The sensation of mechanical stimuli is initiated by elastic gating springs that pull open mechanosensory transduction channels. Searches for gating springs have focused on force-conveying protein tethers such as the amino-terminal ankyrin tether of the <i>Drosophila</i> mechanosensory transduction channel NOMPC. Here, by combining protein domain duplications with mechanical measurements, electrophysiology, molecular dynamics simulations and modeling, we identify the NOMPC gating-spring as the short linker between the ankyrin tether and the channel gate. This linker acts as a Hookean hinge that is ten times more elastic than the tether, with the linker hinge dictating channel gating and the intrinsic stiffness of the gating spring. Our study shows how mechanosensation is initiated molecularly; disentangles gating springs and tethers, and respective paradigms of channel gating; and puts forward gating springs as core ion channel constituents that enable efficient gating by diverse stimuli and in a wide variety of channels.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"8 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929722","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
Cerebellar Bergmann glia integrate noxious information and modulate nocifensive behaviors
IF 25 1区 医学
Nature neuroscience Pub Date : 2025-01-02 DOI: 10.1038/s41593-024-01807-z
Seung Ha Kim, Jaegeon Lee, Mirae Jang, Seung-Eon Roh, Soobin Kim, Ji Hwan Lee, Jewoo Seo, Jinhee Baek, Jae Yoon Hwang, In Seon Baek, Yong-Seok Lee, Eiji Shigetomi, C. Justin Lee, Schuichi Koizumi, Sun Kwang Kim, Sang Jeong Kim
{"title":"Cerebellar Bergmann glia integrate noxious information and modulate nocifensive behaviors","authors":"Seung Ha Kim, Jaegeon Lee, Mirae Jang, Seung-Eon Roh, Soobin Kim, Ji Hwan Lee, Jewoo Seo, Jinhee Baek, Jae Yoon Hwang, In Seon Baek, Yong-Seok Lee, Eiji Shigetomi, C. Justin Lee, Schuichi Koizumi, Sun Kwang Kim, Sang Jeong Kim","doi":"10.1038/s41593-024-01807-z","DOIUrl":"https://doi.org/10.1038/s41593-024-01807-z","url":null,"abstract":"<p>The cerebellum is activated by noxious stimuli and pathological pain but its role in noxious information processing remains unknown. Here, we show that in mice, cutaneous noxious electrical stimuli induced noradrenaline (NA) release from locus coeruleus (LC) terminals in the cerebellar cortex. Bergmann glia (BG) accumulated these LC–NA signals by increasing intracellular calcium in an integrative manner (‘flares’). BG flares were also elicited in response to an intraplantar capsaicin injection. Chemogenetic inactivation of LC terminals or BG in the cerebellar cortex or BG-specific knockdown of α<sub>1</sub>-adrenergic receptors suppressed BG flares, reduced nocifensive licking and had analgesic effects in nerve injury-induced chronic neuropathic pain. Moreover, chemogenetic activation of BG or an intraplantar capsaicin injection reduced Purkinje cell firing, which may disinhibit the output activity of the deep cerebellar nuclei. These results suggest a role for BG in computing noxious information from the LC and in modulating pain-related behaviors by regulating cerebellar output.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"33 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911423","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
Negative self-experiences shape responses to others’ emotional states
IF 21.2 1区 医学
Nature neuroscience Pub Date : 2025-01-02 DOI: 10.1038/s41593-024-01817-x
{"title":"Negative self-experiences shape responses to others’ emotional states","authors":"","doi":"10.1038/s41593-024-01817-x","DOIUrl":"10.1038/s41593-024-01817-x","url":null,"abstract":"Mice react differently to others’ stress depending on their own past experience of the same (but not different) stress. Corticotropin-releasing factor (CRF) neuron activity in the medial prefrontal cortex (mPFC) specifically modulates the influence of affective past experience on emotional reactions to others, which was estrus-dependent in females and dominance-dependent in males.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 1","pages":"11-12"},"PeriodicalIF":21.2,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911421","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
Neurocognitive dynamics of human cooperation unveiled by intracranial recordings
IF 21.2 1区 医学
Nature neuroscience Pub Date : 2025-01-02 DOI: 10.1038/s41593-024-01825-x
{"title":"Neurocognitive dynamics of human cooperation unveiled by intracranial recordings","authors":"","doi":"10.1038/s41593-024-01825-x","DOIUrl":"10.1038/s41593-024-01825-x","url":null,"abstract":"Simultaneous intracranial electroencephalographic recordings from individuals playing a dynamic cooperation game reveal unique neural profiles of high-gamma intra-brain activity and inter-brain synchronization in the temporoparietal junction and the amygdala.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 1","pages":"13-14"},"PeriodicalIF":21.2,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911422","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
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