Pub Date : 2024-09-16DOI: 10.1038/s41593-024-01767-4
Kathleen A. Martin, Eleni S. Papadoyannis, Jennifer K. Schiavo, Saba Shokat Fadaei, Habon A. Issa, Soomin C. Song, Sofia Orrey Valencia, Nesibe Z. Temiz, Matthew J. McGinley, David A. McCormick, Robert C. Froemke
Perception can be refined by experience, up to certain limits. It is unclear whether perceptual limits are absolute or could be partially overcome via enhanced neuromodulation and/or plasticity. Recent studies suggest that peripheral nerve stimulation, specifically vagus nerve stimulation (VNS), can alter neural activity and augment experience-dependent plasticity, although little is known about central mechanisms recruited by VNS. Here we developed an auditory discrimination task for mice implanted with a VNS electrode. VNS applied during behavior gradually improved discrimination abilities beyond the level achieved by training alone. Two-photon imaging revealed VNS induced changes to auditory cortical responses and activated cortically projecting cholinergic axons. Anatomical and optogenetic experiments indicated that VNS can enhance task performance through activation of the central cholinergic system. These results highlight the importance of cholinergic modulation for the efficacy of VNS and may contribute to further refinement of VNS methodology for clinical conditions. Perceptual abilities can be improved by training, up to certain limits. Martin et al. show that vagus nerve stimulation in mice boosts performance on an auditory task via cholinergic modulation, beyond the level achieved by training alone.
{"title":"Vagus nerve stimulation recruits the central cholinergic system to enhance perceptual learning","authors":"Kathleen A. Martin, Eleni S. Papadoyannis, Jennifer K. Schiavo, Saba Shokat Fadaei, Habon A. Issa, Soomin C. Song, Sofia Orrey Valencia, Nesibe Z. Temiz, Matthew J. McGinley, David A. McCormick, Robert C. Froemke","doi":"10.1038/s41593-024-01767-4","DOIUrl":"10.1038/s41593-024-01767-4","url":null,"abstract":"Perception can be refined by experience, up to certain limits. It is unclear whether perceptual limits are absolute or could be partially overcome via enhanced neuromodulation and/or plasticity. Recent studies suggest that peripheral nerve stimulation, specifically vagus nerve stimulation (VNS), can alter neural activity and augment experience-dependent plasticity, although little is known about central mechanisms recruited by VNS. Here we developed an auditory discrimination task for mice implanted with a VNS electrode. VNS applied during behavior gradually improved discrimination abilities beyond the level achieved by training alone. Two-photon imaging revealed VNS induced changes to auditory cortical responses and activated cortically projecting cholinergic axons. Anatomical and optogenetic experiments indicated that VNS can enhance task performance through activation of the central cholinergic system. These results highlight the importance of cholinergic modulation for the efficacy of VNS and may contribute to further refinement of VNS methodology for clinical conditions. Perceptual abilities can be improved by training, up to certain limits. Martin et al. show that vagus nerve stimulation in mice boosts performance on an auditory task via cholinergic modulation, beyond the level achieved by training alone.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 11","pages":"2152-2166"},"PeriodicalIF":21.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234504","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}
Pub Date : 2024-09-12DOI: 10.1038/s41593-024-01754-9
Guojiao Huang, Zhidan Li, Xuezhao Liu, Menglong Guan, Songlin Zhou, Xiaowen Zhong, Tao Zheng, Dazhuan Xin, Xiaosong Gu, Dezhi Mu, Yingkun Guo, Lin Zhang, Liguo Zhang, Q. Richard Lu, Xuelian He
The decreased ability of mature oligodendrocytes to produce myelin negatively affects remyelination in demyelinating diseases and aging, but the underlying mechanisms are incompletely understood. In the present study, we identify a mature oligodendrocyte-enriched transcriptional coregulator diabetes- and obesity-related gene (DOR)/tumor protein p53-inducible nuclear protein 2 (TP53INP2), downregulated in demyelinated lesions of donors with multiple sclerosis and in aged oligodendrocyte-lineage cells. Dor ablation in mice of both sexes results in defective myelinogenesis and remyelination. Genomic occupancy in oligodendrocytes and transcriptome profiling of the optic nerves of wild-type and Dor conditional knockout mice reveal that DOR and SOX10 co-occupy enhancers of critical myelinogenesis-associated genes including Prr18, encoding an oligodendrocyte-enriched, proline-rich factor. We show that DOR targets regulatory elements of genes responsible for α-ketoglutarate biosynthesis in mature oligodendrocytes and is essential for α-ketoglutarate production and lipid biosynthesis. Supplementation with α-ketoglutarate restores oligodendrocyte-maturation defects in Dor-deficient adult mice and improves remyelination after lysolecithin-induced demyelination and cognitive function in 17-month-old wild-type mice. Our data suggest that activation of α-ketoglutarate metabolism in mature oligodendrocytes can promote myelin production during demyelination and aging. The mechanisms underlying the ability to remyelinate in aging and disease are unclear. Here, the authors show that DOR-mediated activation of α-ketoglutarate in mature oligodendrocytes can promote myelin production in mice during demyelination and aging.
成熟少突胶质细胞产生髓鞘的能力下降会对脱髓鞘疾病和衰老中的再髓鞘化产生负面影响，但其潜在机制尚不完全清楚。在本研究中，我们发现了一个成熟少突胶质细胞富集的转录核心调节因子糖尿病和肥胖相关基因（DOR）/肿瘤蛋白 p53 诱导核蛋白 2（TP53INP2），它在多发性硬化症供体的脱髓鞘病变和衰老的少突胶质细胞系细胞中下调。小鼠（雌雄均可）的髓鞘消融导致髓鞘生成和再髓鞘化缺陷。野生型小鼠和 Dor 条件性基因敲除小鼠视神经中的少突胶质细胞基因组占位和转录组图谱分析表明，DOR 和 SOX10 共同占据了关键的髓鞘生成相关基因的增强子，包括 Prr18（编码一种富含脯氨酸的少突胶质细胞因子）。我们的研究表明，DOR靶向成熟少突胶质细胞中负责α-酮戊二酸生物合成的基因的调控元件，并且对α-酮戊二酸的产生和脂质的生物合成至关重要。补充α-酮戊二酸可恢复Dor缺陷成年小鼠少突胶质细胞成熟缺陷，并改善溶血卵磷脂诱导脱髓鞘后的再髓鞘化和17个月大野生型小鼠的认知功能。我们的数据表明，激活成熟少突胶质细胞中的α-酮戊二酸代谢可促进脱髓鞘和衰老过程中的髓鞘生成。
{"title":"DOR activation in mature oligodendrocytes regulates α-ketoglutarate metabolism leading to enhanced remyelination in aged mice","authors":"Guojiao Huang, Zhidan Li, Xuezhao Liu, Menglong Guan, Songlin Zhou, Xiaowen Zhong, Tao Zheng, Dazhuan Xin, Xiaosong Gu, Dezhi Mu, Yingkun Guo, Lin Zhang, Liguo Zhang, Q. Richard Lu, Xuelian He","doi":"10.1038/s41593-024-01754-9","DOIUrl":"10.1038/s41593-024-01754-9","url":null,"abstract":"The decreased ability of mature oligodendrocytes to produce myelin negatively affects remyelination in demyelinating diseases and aging, but the underlying mechanisms are incompletely understood. In the present study, we identify a mature oligodendrocyte-enriched transcriptional coregulator diabetes- and obesity-related gene (DOR)/tumor protein p53-inducible nuclear protein 2 (TP53INP2), downregulated in demyelinated lesions of donors with multiple sclerosis and in aged oligodendrocyte-lineage cells. Dor ablation in mice of both sexes results in defective myelinogenesis and remyelination. Genomic occupancy in oligodendrocytes and transcriptome profiling of the optic nerves of wild-type and Dor conditional knockout mice reveal that DOR and SOX10 co-occupy enhancers of critical myelinogenesis-associated genes including Prr18, encoding an oligodendrocyte-enriched, proline-rich factor. We show that DOR targets regulatory elements of genes responsible for α-ketoglutarate biosynthesis in mature oligodendrocytes and is essential for α-ketoglutarate production and lipid biosynthesis. Supplementation with α-ketoglutarate restores oligodendrocyte-maturation defects in Dor-deficient adult mice and improves remyelination after lysolecithin-induced demyelination and cognitive function in 17-month-old wild-type mice. Our data suggest that activation of α-ketoglutarate metabolism in mature oligodendrocytes can promote myelin production during demyelination and aging. The mechanisms underlying the ability to remyelinate in aging and disease are unclear. Here, the authors show that DOR-mediated activation of α-ketoglutarate in mature oligodendrocytes can promote myelin production in mice during demyelination and aging.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 11","pages":"2073-2085"},"PeriodicalIF":21.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170841","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}
Pub Date : 2024-09-12DOI: 10.1038/s41593-024-01750-z
We reveal that lipid turnover in the myelin sheath generates a fatty acid pool in oligodendrocytes that can contribute to the energy balance of white matter tracts. We also demonstrate that when glucose levels are limiting, fatty acid metabolism can support glial cell survival and the basic functional integrity of myelinated axons.
{"title":"Myelin lipid metabolism can provide energy for starved axons","authors":"","doi":"10.1038/s41593-024-01750-z","DOIUrl":"10.1038/s41593-024-01750-z","url":null,"abstract":"We reveal that lipid turnover in the myelin sheath generates a fatty acid pool in oligodendrocytes that can contribute to the energy balance of white matter tracts. We also demonstrate that when glucose levels are limiting, fatty acid metabolism can support glial cell survival and the basic functional integrity of myelinated axons.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 10","pages":"1862-1863"},"PeriodicalIF":21.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142175023","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}
Pub Date : 2024-09-10DOI: 10.1038/s41593-024-01746-9
Sanjid Shahriar, Saptarshi Biswas, Kaitao Zhao, Uğur Akcan, Mary Claire Tuohy, Michael D. Glendinning, Ali Kurt, Charlotte R. Wayne, Grace Prochilo, Maxwell Z. Price, Heidi Stuhlmann, Rolf A. Brekken, Vilas Menon, Dritan Agalliu
Newly formed leaky vessels and blood–brain barrier (BBB) damage are present in demyelinating acute and chronic lesions in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). However, the endothelial cell subtypes and signaling pathways contributing to these leaky neovessels are unclear. Here, using single-cell transcriptional profiling and in vivo validation studies, we show that venous endothelial cells express neoangiogenesis gene signatures and show increased proliferation resulting in enlarged veins and higher venous coverage in acute and chronic EAE lesions in female adult mice. These changes correlate with the upregulation of vascular endothelial growth factor A (VEGF-A) signaling. We also confirmed increased expression of neoangiogenic markers in acute and chronic human MS lesions. Treatment with a VEGF-A blocking antibody diminishes the neoangiogenic transcriptomic signatures and vascular proliferation in female adult mice with EAE, but it does not restore BBB function or ameliorate EAE pathology. Our data demonstrate that venous endothelial cells contribute to neoangiogenesis in demyelinating neuroinflammatory conditions. Defective neoangiogenesis and blood–brain barrier leakiness are pathological hallmarks of neuroinflammation. Here the authors show that vascular endothelial growth factor A (VEGF-A) promotes venous endothelial cell proliferation, resulting in the formation of leaky vessels around demyelinating lesions in multiple sclerosis and experimental autoimmune encephalomyelitis.
{"title":"VEGF-A-mediated venous endothelial cell proliferation results in neoangiogenesis during neuroinflammation","authors":"Sanjid Shahriar, Saptarshi Biswas, Kaitao Zhao, Uğur Akcan, Mary Claire Tuohy, Michael D. Glendinning, Ali Kurt, Charlotte R. Wayne, Grace Prochilo, Maxwell Z. Price, Heidi Stuhlmann, Rolf A. Brekken, Vilas Menon, Dritan Agalliu","doi":"10.1038/s41593-024-01746-9","DOIUrl":"10.1038/s41593-024-01746-9","url":null,"abstract":"Newly formed leaky vessels and blood–brain barrier (BBB) damage are present in demyelinating acute and chronic lesions in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). However, the endothelial cell subtypes and signaling pathways contributing to these leaky neovessels are unclear. Here, using single-cell transcriptional profiling and in vivo validation studies, we show that venous endothelial cells express neoangiogenesis gene signatures and show increased proliferation resulting in enlarged veins and higher venous coverage in acute and chronic EAE lesions in female adult mice. These changes correlate with the upregulation of vascular endothelial growth factor A (VEGF-A) signaling. We also confirmed increased expression of neoangiogenic markers in acute and chronic human MS lesions. Treatment with a VEGF-A blocking antibody diminishes the neoangiogenic transcriptomic signatures and vascular proliferation in female adult mice with EAE, but it does not restore BBB function or ameliorate EAE pathology. Our data demonstrate that venous endothelial cells contribute to neoangiogenesis in demyelinating neuroinflammatory conditions. Defective neoangiogenesis and blood–brain barrier leakiness are pathological hallmarks of neuroinflammation. Here the authors show that vascular endothelial growth factor A (VEGF-A) promotes venous endothelial cell proliferation, resulting in the formation of leaky vessels around demyelinating lesions in multiple sclerosis and experimental autoimmune encephalomyelitis.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 10","pages":"1904-1917"},"PeriodicalIF":21.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160457","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}
Pub Date : 2024-09-09DOI: 10.1038/s41593-024-01749-6
Ebrahim Asadollahi, Andrea Trevisiol, Aiman S. Saab, Zoe J. Looser, Payam Dibaj, Reyhane Ebrahimi, Kathrin Kusch, Torben Ruhwedel, Wiebke Möbius, Olaf Jahn, Jun Yup Lee, Anthony S. Don, Michelle-Amirah Khalil, Karsten Hiller, Myriam Baes, Bruno Weber, E. Dale Abel, Andrea Ballabio, Brian Popko, Celia M. Kassmann, Hannelore Ehrenreich, Johannes Hirrlinger, Klaus-Armin Nave
Brain function requires a constant supply of glucose. However, the brain has no known energy stores, except for glycogen granules in astrocytes. In the present study, we report that continuous oligodendroglial lipid metabolism provides an energy reserve in white matter tracts. In the isolated optic nerve from young adult mice of both sexes, oligodendrocytes survive glucose deprivation better than astrocytes. Under low glucose, both axonal ATP levels and action potentials become dependent on fatty acid β-oxidation. Importantly, ongoing oligodendroglial lipid degradation feeds rapidly into white matter energy metabolism. Although not supporting high-frequency spiking, fatty acid β-oxidation in mitochondria and oligodendroglial peroxisomes protects axons from conduction blocks when glucose is limiting. Disruption of the glucose transporter GLUT1 expression in oligodendrocytes of adult mice perturbs myelin homeostasis in vivo and causes gradual demyelination without behavioral signs. This further suggests that the imbalance of myelin synthesis and degradation can underlie myelin thinning in aging and disease. Brain functions require a constant supply of glucose. However, the brain energy stores are unclear. Here, the authors show that oligodendroglial fatty acid metabolism can be an energy reserve for white matter axons, supporting their function.
大脑功能需要葡萄糖的持续供应。然而，除了星形胶质细胞中的糖原颗粒外，大脑没有已知的能量储备。在本研究中，我们报告了持续的少突胶质细胞脂质代谢为白质束提供了能量储备。在离体的成年雌雄小鼠视神经中，少突胶质细胞比星形胶质细胞更能在葡萄糖剥夺中存活。在低葡萄糖条件下，轴突的 ATP 水平和动作电位都依赖于脂肪酸的β-氧化。重要的是，持续的少突胶质细胞脂质降解会迅速影响白质的能量代谢。线粒体和少突胶质细胞过氧体中的脂肪酸β-氧化虽然不能支持高频尖峰脉冲，但却能在葡萄糖受限时保护轴突免受传导阻滞。成年小鼠少突胶质细胞中葡萄糖转运体 GLUT1 的表达中断会扰乱体内髓鞘的稳态，并导致逐渐脱髓鞘而无行为症状。这进一步表明，髓鞘合成和降解的失衡可能是衰老和疾病导致髓鞘变薄的原因。
{"title":"Oligodendroglial fatty acid metabolism as a central nervous system energy reserve","authors":"Ebrahim Asadollahi, Andrea Trevisiol, Aiman S. Saab, Zoe J. Looser, Payam Dibaj, Reyhane Ebrahimi, Kathrin Kusch, Torben Ruhwedel, Wiebke Möbius, Olaf Jahn, Jun Yup Lee, Anthony S. Don, Michelle-Amirah Khalil, Karsten Hiller, Myriam Baes, Bruno Weber, E. Dale Abel, Andrea Ballabio, Brian Popko, Celia M. Kassmann, Hannelore Ehrenreich, Johannes Hirrlinger, Klaus-Armin Nave","doi":"10.1038/s41593-024-01749-6","DOIUrl":"10.1038/s41593-024-01749-6","url":null,"abstract":"Brain function requires a constant supply of glucose. However, the brain has no known energy stores, except for glycogen granules in astrocytes. In the present study, we report that continuous oligodendroglial lipid metabolism provides an energy reserve in white matter tracts. In the isolated optic nerve from young adult mice of both sexes, oligodendrocytes survive glucose deprivation better than astrocytes. Under low glucose, both axonal ATP levels and action potentials become dependent on fatty acid β-oxidation. Importantly, ongoing oligodendroglial lipid degradation feeds rapidly into white matter energy metabolism. Although not supporting high-frequency spiking, fatty acid β-oxidation in mitochondria and oligodendroglial peroxisomes protects axons from conduction blocks when glucose is limiting. Disruption of the glucose transporter GLUT1 expression in oligodendrocytes of adult mice perturbs myelin homeostasis in vivo and causes gradual demyelination without behavioral signs. This further suggests that the imbalance of myelin synthesis and degradation can underlie myelin thinning in aging and disease. Brain functions require a constant supply of glucose. However, the brain energy stores are unclear. Here, the authors show that oligodendroglial fatty acid metabolism can be an energy reserve for white matter axons, supporting their function.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 10","pages":"1934-1944"},"PeriodicalIF":21.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01749-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158972","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}
Pub Date : 2024-09-06DOI: 10.1038/s41593-024-01731-2
Omid G. Sani, Bijan Pesaran, Maryam M. Shanechi
Understanding the dynamical transformation of neural activity to behavior requires new capabilities to nonlinearly model, dissociate and prioritize behaviorally relevant neural dynamics and test hypotheses about the origin of nonlinearity. We present dissociative prioritized analysis of dynamics (DPAD), a nonlinear dynamical modeling approach that enables these capabilities with a multisection neural network architecture and training approach. Analyzing cortical spiking and local field potential activity across four movement tasks, we demonstrate five use-cases. DPAD enabled more accurate neural–behavioral prediction. It identified nonlinear dynamical transformations of local field potentials that were more behavior predictive than traditional power features. Further, DPAD achieved behavior-predictive nonlinear neural dimensionality reduction. It enabled hypothesis testing regarding nonlinearities in neural–behavioral transformation, revealing that, in our datasets, nonlinearities could largely be isolated to the mapping from latent cortical dynamics to behavior. Finally, DPAD extended across continuous, intermittently sampled and categorical behaviors. DPAD provides a powerful tool for nonlinear dynamical modeling and investigation of neural–behavioral data. The authors present DPAD, a deep learning method, for dynamical neural–behavioral modeling. It dissociates behaviorally relevant neural dynamics, better predicts neural–behavioral data and reveals insight into where their nonlinearities can be isolated.
{"title":"Dissociative and prioritized modeling of behaviorally relevant neural dynamics using recurrent neural networks","authors":"Omid G. Sani, Bijan Pesaran, Maryam M. Shanechi","doi":"10.1038/s41593-024-01731-2","DOIUrl":"10.1038/s41593-024-01731-2","url":null,"abstract":"Understanding the dynamical transformation of neural activity to behavior requires new capabilities to nonlinearly model, dissociate and prioritize behaviorally relevant neural dynamics and test hypotheses about the origin of nonlinearity. We present dissociative prioritized analysis of dynamics (DPAD), a nonlinear dynamical modeling approach that enables these capabilities with a multisection neural network architecture and training approach. Analyzing cortical spiking and local field potential activity across four movement tasks, we demonstrate five use-cases. DPAD enabled more accurate neural–behavioral prediction. It identified nonlinear dynamical transformations of local field potentials that were more behavior predictive than traditional power features. Further, DPAD achieved behavior-predictive nonlinear neural dimensionality reduction. It enabled hypothesis testing regarding nonlinearities in neural–behavioral transformation, revealing that, in our datasets, nonlinearities could largely be isolated to the mapping from latent cortical dynamics to behavior. Finally, DPAD extended across continuous, intermittently sampled and categorical behaviors. DPAD provides a powerful tool for nonlinear dynamical modeling and investigation of neural–behavioral data. The authors present DPAD, a deep learning method, for dynamical neural–behavioral modeling. It dissociates behaviorally relevant neural dynamics, better predicts neural–behavioral data and reveals insight into where their nonlinearities can be isolated.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 10","pages":"2033-2045"},"PeriodicalIF":21.2,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01731-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142733","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}
Pub Date : 2024-09-05DOI: 10.1038/s41593-024-01759-4
Elisa Floriddia
{"title":"Molecular architecture of the human brain vasculature","authors":"Elisa Floriddia","doi":"10.1038/s41593-024-01759-4","DOIUrl":"10.1038/s41593-024-01759-4","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 9","pages":"1638-1638"},"PeriodicalIF":21.2,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140625","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}
Pub Date : 2024-09-05DOI: 10.1038/s41593-024-01762-9
Nature Neuroscience now welcomes Registered Reports — a publishing format designed to prioritize methodological rigor.
自然-神经科学》现在欢迎注册报告--一种旨在优先考虑方法严谨性的出版格式。
{"title":"Reducing publication bias with Registered Reports","authors":"","doi":"10.1038/s41593-024-01762-9","DOIUrl":"10.1038/s41593-024-01762-9","url":null,"abstract":"Nature Neuroscience now welcomes Registered Reports — a publishing format designed to prioritize methodological rigor.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 9","pages":"1635-1635"},"PeriodicalIF":21.2,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01762-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140626","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}
Pub Date : 2024-09-05DOI: 10.1038/s41593-024-01748-7
Jessie Muir, Eshaan S. Iyer, Yiu-Chung Tse, Julian Sorensen, Serena Wu, Rand S. Eid, Vedrana Cvetkovska, Karen Wassef, Sarah Gostlin, Peter Vitaro, Nick J. Spencer, Rosemary C. Bagot
Learning to predict threat is essential, but equally important—yet often overlooked—is learning about the absence of threat. Here, by recording neural activity in two nucleus accumbens (NAc) glutamatergic afferents during aversive and neutral cues, we reveal sex-biased encoding of threat cue discrimination. In male mice, NAc afferents from the ventral hippocampus are preferentially activated by threat cues. In female mice, these ventral hippocampus–NAc projections are activated by both threat and nonthreat cues, whereas NAc afferents from medial prefrontal cortex are more strongly recruited by footshock and reliably discriminate threat from nonthreat. Chemogenetic pathway-specific inhibition identifies a double dissociation between ventral hippocampus–NAc and medial prefrontal cortex–NAc projections in cue-mediated suppression of reward-motivated behavior in male and female mice, despite similar synaptic connectivity. We suggest that these sex biases may reflect sex differences in behavioral strategies that may have relevance for understanding sex differences in risk of psychiatric disorders. Muir et al. explore threat discrimination in male and female mice and find that, despite similar behavioral acquisition, there are surprising sex differences in the neural encoding that drives suppression of reward seeking under threat.
{"title":"Sex-biased neural encoding of threat discrimination in nucleus accumbens afferents drives suppression of reward behavior","authors":"Jessie Muir, Eshaan S. Iyer, Yiu-Chung Tse, Julian Sorensen, Serena Wu, Rand S. Eid, Vedrana Cvetkovska, Karen Wassef, Sarah Gostlin, Peter Vitaro, Nick J. Spencer, Rosemary C. Bagot","doi":"10.1038/s41593-024-01748-7","DOIUrl":"10.1038/s41593-024-01748-7","url":null,"abstract":"Learning to predict threat is essential, but equally important—yet often overlooked—is learning about the absence of threat. Here, by recording neural activity in two nucleus accumbens (NAc) glutamatergic afferents during aversive and neutral cues, we reveal sex-biased encoding of threat cue discrimination. In male mice, NAc afferents from the ventral hippocampus are preferentially activated by threat cues. In female mice, these ventral hippocampus–NAc projections are activated by both threat and nonthreat cues, whereas NAc afferents from medial prefrontal cortex are more strongly recruited by footshock and reliably discriminate threat from nonthreat. Chemogenetic pathway-specific inhibition identifies a double dissociation between ventral hippocampus–NAc and medial prefrontal cortex–NAc projections in cue-mediated suppression of reward-motivated behavior in male and female mice, despite similar synaptic connectivity. We suggest that these sex biases may reflect sex differences in behavioral strategies that may have relevance for understanding sex differences in risk of psychiatric disorders. Muir et al. explore threat discrimination in male and female mice and find that, despite similar behavioral acquisition, there are surprising sex differences in the neural encoding that drives suppression of reward seeking under threat.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 10","pages":"1966-1976"},"PeriodicalIF":21.2,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142137992","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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