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Sustained EEG responses to rapidly unfolding stochastic sounds reflect Bayesian inferred reliability tracking 对快速展开的随机声音的持续脑电图反应反映了贝叶斯推断的可靠性跟踪。
IF 6.7 2区 医学 Q1 NEUROSCIENCES Pub Date : 2025-01-01 DOI: 10.1016/j.pneurobio.2024.102696
Sijia Zhao , Benjamin Skerritt-Davis , Mounya Elhilali , Frederic Dick , Maria Chait
How does the brain track and process rapidly changing sensory information? Current computational accounts suggest that our sensations and decisions arise from the intricate interplay between bottom-up sensory signals and constantly changing expectations regarding the statistics of the surrounding world. A significant focus of recent research is determining which statistical properties are tracked by the brain as it monitors the rapid progression of sensory information. Here, by combining EEG (three experiments N ≥ 22 each) and computational modelling, we examined how the brain processes rapid and stochastic sound sequences that simulate key aspects of dynamic sensory environments. Passively listening participants were exposed to structured tone-pip arrangements that contained transitions between a range of stochastic patterns. Predictions were guided by a Bayesian predictive inference model. We demonstrate that listeners automatically track the statistics of unfolding sounds, even when these are irrelevant to behaviour. Transitions between sequence patterns drove a shift in the sustained EEG response. This was observed to a range of distributional statistics, and even in situations where behavioural detection of these transitions was at floor. These observations suggest that the modulation of the EEG sustained response reflects a process of belief updating within the brain. By establishing a connection between the outputs of the computational model and the observed brain responses, we demonstrate that the dynamics of these transition-related responses align with the tracking of “precision” – the confidence or reliability assigned to a predicted sensory signal - shedding light on the intricate interplay between the brain's statistical tracking mechanisms and its response dynamics.
大脑是如何追踪和处理快速变化的感官信息的?目前的计算表明,我们的感觉和决定来自于自下而上的感官信号和对周围世界的统计数据不断变化的预期之间复杂的相互作用。最近研究的一个重要焦点是确定大脑在监控感官信息的快速发展时跟踪了哪些统计特性。在这里,通过结合EEG(每个实验N≥22)和计算模型,我们研究了大脑如何处理模拟动态感官环境关键方面的快速和随机声音序列。被动倾听的参与者被暴露在结构化的音调-pip安排中,其中包含一系列随机模式之间的转换。预测由贝叶斯预测推理模型指导。我们证明了听者会自动跟踪展开声音的统计数据,即使这些声音与行为无关。序列模式之间的转换导致持续脑电图反应的增加。这被观察到分布统计的范围,甚至在这些过渡的行为检测是在地板的情况下。这些观察结果表明,脑电图持续反应的调节反映了大脑内信念更新的过程。通过建立计算模型的输出和观察到的大脑反应之间的联系,我们证明了这些与过渡相关的反应的动态与“精度”的跟踪一致-分配给预测感官信号的置信度或可靠性-揭示了大脑统计跟踪机制与其反应动力学之间复杂的相互作用。
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引用次数: 0
Decade of TRAP progress: Insights and future prospects for advancing functional network research in epilepsy TRAP进展的十年:癫痫功能网络研究的见解和未来展望。
IF 6.7 2区 医学 Q1 NEUROSCIENCES Pub Date : 2025-01-01 DOI: 10.1016/j.pneurobio.2024.102707
Zhisheng Li , Wangjialu Lu , Lin Yang , Nanxi Lai , Yi Wang , Zhong Chen
Targeted Recombination in Active Populations (TRAP) represents an effective and extensively applied technique that has earned significant utilization in neuroscience over the past decade, primarily for identifying and modulating functionally activated neuronal ensembles associated with diverse behaviors. As epilepsy is a neurological disorder characterized by pathological hyper-excitatory networks, TRAP has already been widely applied in epilepsy research. However, the deployment of TRAP in this field remains underexplored, and there is significant potential for further application and development in epilepsy-related investigations. In this review, we embark on a concise examination of the mechanisms behind several TRAP tools, introduce the current applications of TRAP in epilepsy research, and collate the key advantages as well as limitations of TRAP. Furthermore, we sketch out perspectives on potential applications of TRAP in future epilepsy research, grounded in the present landscape and challenges of the field, as well as the ways TRAP has been embraced in other neuroscience domains.
活性群体中的靶向重组(TRAP)是一种有效且广泛应用的技术,在过去十年中在神经科学中获得了显著的应用,主要用于识别和调节与不同行为相关的功能激活神经元集合。由于癫痫是一种以病理性超兴奋网络为特征的神经系统疾病,TRAP已广泛应用于癫痫研究。然而,TRAP在这一领域的应用仍未得到充分探索,在癫痫相关调查中有进一步应用和发展的巨大潜力。在这篇综述中,我们将简要介绍几种TRAP工具背后的机制,介绍TRAP在癫痫研究中的当前应用,并整理TRAP的主要优势和局限性。此外,我们概述了TRAP在未来癫痫研究中的潜在应用前景,基于该领域的现状和挑战,以及TRAP在其他神经科学领域的应用方式。
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引用次数: 0
Prefrontal excitation/inhibition balance supports adolescent enhancements in circuit signal to noise ratio 前额叶激励/抑制平衡支持青春期电路信噪比的增强。
IF 6.7 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-12-01 DOI: 10.1016/j.pneurobio.2024.102695
Shane D. McKeon , Maria I. Perica , Finnegan J. Calabro , Will Foran , Hoby Hetherington , Chan-Hong Moon , Beatriz Luna
The development and refinement of neuronal circuitry allow for stabilized and efficient neural recruitment, supporting adult-like behavioral performance. During adolescence, the maturation of PFC is proposed to be a critical period (CP) for executive function, driven by a break in balance between glutamatergic excitation and GABAergic inhibition (E/I) neurotransmission. During CPs, cortical circuitry fine-tunes to improve information processing and reliable responses to stimuli, shifting from spontaneous to evoked activity, enhancing the SNR, and promoting neural synchronization. Harnessing 7 T MR spectroscopy and EEG in a longitudinal cohort (N = 164, ages 10–32 years, 283 neuroimaging sessions), we outline associations between age-related changes in glutamate and GABA neurotransmitters and EEG measures of cortical SNR. We find developmental decreases in spontaneous activity and increases in cortical SNR during our auditory steady state task using 40 Hz stimuli. Decreases in spontaneous activity were associated with glutamate levels in DLPFC, while increases in cortical SNR were associated with more balanced Glu and GABA levels. These changes were associated with improvements in working memory performance. This study provides evidence of CP plasticity in the human PFC during adolescence, leading to stabilized circuitry that allows for the optimal recruitment and integration of multisensory input, resulting in improved executive function.
神经回路的发展和完善允许稳定和有效的神经招募,支持类似成人的行为表现。在青春期,PFC的成熟被认为是执行功能的关键时期(CP),由谷氨酸能兴奋和GABAergic抑制(E/I)神经传递之间的平衡被打破所驱动。在CPs过程中,皮层回路微调以改善信息处理和对刺激的可靠反应,从自发活动转向诱发活动,增强信噪比,促进神经同步。利用7T磁共振波谱和脑电图纵向队列(N = 164,年龄10-32岁,283次神经成像),我们概述了谷氨酸和GABA神经递质的年龄相关变化与皮层信噪比的脑电图测量之间的关系。我们发现在使用40Hz刺激的听觉稳态任务中,自发活动的发育减少和皮层信噪比的增加。自发性活动的减少与DLPFC中的谷氨酸水平有关,而皮质信噪比的增加与谷氨酸和氨基丁酸水平更平衡有关。这些变化与工作记忆表现的改善有关。这项研究提供了青春期人类PFC的CP可塑性的证据,导致稳定的电路,允许最佳的多感觉输入的招募和整合,从而改善执行功能。
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引用次数: 0
The primate putamen processes cognitive flexibility alongside the caudate and ventral striatum with similar speeds of updating values 灵长类动物壳核与尾状体和腹侧纹状体一起处理认知灵活性,更新值的速度相似。
IF 6.7 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-12-01 DOI: 10.1016/j.pneurobio.2024.102651
Shin-young An , Seong-Hwan Hwang , Keonwoo Lee, Hyoung F. Kim
The putamen is thought to generate habitual actions by processing value information relayed from the ventral striatum through the caudate nucleus. However, it is a question what value the putamen neurons process and whether the putamen receives serially processed value through the striatal structures. We found that neurons in the primate putamen, caudate, and ventral striatum selectively encoded flexibly updated values for adaptive behaviors with similar learning speeds, rather than stably sustained values for habit. In reversal value learning, rostral striatum neurons dynamically adjusted their responses to object values in alignment with changes in saccade reaction times following reversals. Notably, the value acquisition speeds within trials were similar, proposing a parallel value update in each striatal region. However, in stable value retrieval, most did not encode the values for habitual saccades. Our findings suggest that the rostral striatum including the putamen is selectively involved in the parallel processing of cognitive flexibility.
壳核被认为是通过处理从腹侧纹状体传递到尾状核的价值信息来产生习惯性行为的。然而,壳核神经元处理的是什么值,以及壳核是否通过纹状体结构接受连续处理的值是一个问题。我们发现灵长类动物壳核、尾状体和腹侧纹状体中的神经元选择性地编码具有相似学习速度的适应性行为的灵活更新值,而不是稳定持续的习惯值。在反向值学习中,吻侧纹状体神经元动态调整其对物体值的反应,与反转后扫视反应时间的变化保持一致。值得注意的是,实验中的值获取速度是相似的,这表明每个纹状体区域都有平行的值更新。然而,在稳定值检索中,大多数不编码习惯性扫视的值。我们的研究结果表明,吻侧纹状体包括壳核选择性地参与了认知灵活性的平行加工。
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引用次数: 0
Microproteins encoded by short open reading frames: Vital regulators in neurological diseases 短开放阅读框编码的微蛋白:神经系统疾病中的重要调节因子
IF 6.7 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-11-23 DOI: 10.1016/j.pneurobio.2024.102694
Xiao Xiao , Yitian Wang , Tingyu Li , Qiang Wang , Xiaolei Luo , Jingdong Li , Linbo Gao
Short open reading frames (sORFs) are frequently overlooked because of their historical classification as non-coding elements or dismissed as “transcriptional noise”. However, advanced genomic and proteomic technologies have allowed for screening and validating sORFs-encoded peptides, revealing their fundamental regulatory roles in cellular processes and sparking a growing interest in microprotein biology. In neuroscience, microproteins serve as neurotransmitters in signal transmission and regulate metabolism and emotions, exerting pivotal effects on neurological conditions such as nerve injury, neurogenic tumors, inflammation, and neurodegenerative diseases. This review summarizes the origins, characteristics, classifications, and functions of microproteins, focusing on their molecular mechanisms in neurological disorders. Potential applications, future perspectives, and challenges are discussed.
短开放阅读框(sORFs)由于历来被归类为非编码元素或被视为 "转录噪音 "而经常被忽视。然而,先进的基因组学和蛋白质组学技术已经能够筛选和验证 sORFs 编码的肽,揭示它们在细胞过程中的基本调控作用,并激发了人们对微量蛋白质生物学的兴趣。在神经科学领域,微蛋白在信号传递过程中充当神经递质,并调节新陈代谢和情绪,对神经损伤、神经源性肿瘤、炎症和神经退行性疾病等神经系统疾病有着举足轻重的影响。这篇综述总结了微蛋白的起源、特点、分类和功能,重点探讨了它们在神经系统疾病中的分子机制。文章还讨论了微蛋白的潜在应用、未来前景和挑战。
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引用次数: 0
Purinergic-associated immune responses in neurodegenerative diseases 神经退行性疾病中与嘌呤能相关的免疫反应。
IF 6.7 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-11-22 DOI: 10.1016/j.pneurobio.2024.102693
Sara Carracedo , Agathe Launay , Paul-Alexandre Dechelle-Marquet , Emilie Faivre , David Blum , Cécile Delarasse , Eric Boué-Grabot
The chronic activation of immune cells can participate in the development of pathological conditions such as neurodegenerative diseases including Alzheimer’s disease (AD), Multiple Sclerosis (MS), Parkinson’s disease (PD), Huntington’s disease (HD) and Amyotrophic Lateral Sclerosis (ALS).
In recent years, compelling evidence indicates that purinergic signaling plays a key role in neuro-immune cell functions. The extracellular release of adenosine 5′-triphosphate (ATP), and its breakdown products (ADP and adenosine) provide the versatile basis for complex purinergic signaling through the activation of several families of receptors. G-protein coupled adenosine A2A receptors, ionotropic P2X and G-protein coupled P2Y receptors for ATP and other nucleotides are abundant and widely distributed in neurons, microglia, and astrocytes of the central nervous system as well as in peripheral immune cells. These receptors are strongly linked to inflammation, with a functional interplay that may influence the intricate purinergic signaling involved in inflammatory responses.
In the present review, we examine the roles of the purinergic receptors in neuro-immune cell functions with particular emphasis on A2AR, P2X4 and P2X7 and their possible relevance to specific neurodegenerative disorders. Understanding the molecular mechanisms governing purinergic receptor interaction will be crucial for advancing the development of effective immunotherapies targeting neurodegenerative diseases.
免疫细胞的慢性激活可参与神经退行性疾病(包括阿尔茨海默病(AD)、多发性硬化症(MS)、帕金森病(PD)、亨廷顿病(HD)和肌萎缩侧索硬化症(ALS))等病症的发展。近年来,令人信服的证据表明,嘌呤能信号在神经免疫细胞功能中发挥着关键作用。细胞外释放的 5'-三磷酸腺苷(ATP)及其分解产物(ADP 和腺苷)通过激活多个受体家族,为复杂的嘌呤能信号传导提供了多功能基础。G蛋白偶联腺苷A2A受体、离子型P2X受体和G蛋白偶联P2Y受体可产生ATP和其他核苷酸,它们在中枢神经系统的神经元、小胶质细胞和星形胶质细胞以及外周免疫细胞中含量丰富,分布广泛。这些受体与炎症密切相关,其功能相互作用可能会影响炎症反应中错综复杂的嘌呤能信号转导。在本综述中,我们将研究嘌呤能受体在神经免疫细胞功能中的作用,尤其侧重于 A2AR、P2X4 和 P2X7 及其与特定神经退行性疾病的可能相关性。了解嘌呤能受体相互作用的分子机制对于促进开发针对神经退行性疾病的有效免疫疗法至关重要。
{"title":"Purinergic-associated immune responses in neurodegenerative diseases","authors":"Sara Carracedo ,&nbsp;Agathe Launay ,&nbsp;Paul-Alexandre Dechelle-Marquet ,&nbsp;Emilie Faivre ,&nbsp;David Blum ,&nbsp;Cécile Delarasse ,&nbsp;Eric Boué-Grabot","doi":"10.1016/j.pneurobio.2024.102693","DOIUrl":"10.1016/j.pneurobio.2024.102693","url":null,"abstract":"<div><div>The chronic activation of immune cells can participate in the development of pathological conditions such as neurodegenerative diseases including Alzheimer’s disease (AD), Multiple Sclerosis (MS), Parkinson’s disease (PD), Huntington’s disease (HD) and Amyotrophic Lateral Sclerosis (ALS).</div><div>In recent years, compelling evidence indicates that purinergic signaling plays a key role in neuro-immune cell functions. The extracellular release of adenosine 5′-triphosphate (ATP), and its breakdown products (ADP and adenosine) provide the versatile basis for complex purinergic signaling through the activation of several families of receptors. G-protein coupled adenosine A<sub>2A</sub> receptors, ionotropic P2X and G-protein coupled P2Y receptors for ATP and other nucleotides are abundant and widely distributed in neurons, microglia, and astrocytes of the central nervous system as well as in peripheral immune cells. These receptors are strongly linked to inflammation, with a functional interplay that may influence the intricate purinergic signaling involved in inflammatory responses.</div><div>In the present review, we examine the roles of the purinergic receptors in neuro-immune cell functions with particular emphasis on A<sub>2A</sub>R, P2X4 and P2X7 and their possible relevance to specific neurodegenerative disorders. Understanding the molecular mechanisms governing purinergic receptor interaction will be crucial for advancing the development of effective immunotherapies targeting neurodegenerative diseases.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"243 ","pages":"Article 102693"},"PeriodicalIF":6.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Receptor-dependent influence of R7 RGS proteins on neuronal GIRK channel signaling dynamics R7 RGS 蛋白对神经元 GIRK 通道信号动态的受体依赖性影响
IF 6.7 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-11-13 DOI: 10.1016/j.pneurobio.2024.102686
Haichang Luo , Allison Anderson , Ikuo Masuho , Ezequiel Marron Fernandez de Velasco , Lutz Birnbaumer , Kirill A. Martemyanov , Kevin Wickman
Most neurons are influenced by multiple neuromodulatory inputs that converge on common effectors. Mechanisms that route these signals are key to selective neuromodulation but are poorly understood. G protein-gated inwardly rectifying K+ (GIRK or Kir3) channels mediate postsynaptic inhibition evoked by G protein-coupled receptors (GPCRs) that signal via inhibitory G proteins. GIRK-dependent signaling is modulated by Regulator of G protein Signaling proteins RGS6 and RGS7, but their selectivity for distinct GPCR-GIRK signaling pathways in defined neurons is unclear. We compared how RGS6 and RGS7 impact GIRK channel regulation by the GABAB receptor (GABABR), 5HT1A receptor (5HT1AR), and A1 adenosine receptor (A1R) in hippocampal neurons. Our data show that RGS6 and RGS7 make non-redundant contributions to GABABR- and 5HT1AR-GIRK signaling and compartmentalization and suggest that GPCR-G protein preferences and the substrate bias of RGS proteins, as well as receptor-dependent differences in Gαo engagement and effector access, shape GPCR-GIRK signaling dynamics in hippocampal neurons.
大多数神经元都会受到多种神经调节输入信号的影响,这些信号会汇聚到共同的效应器上。这些信号的传递机制是选择性神经调节的关键,但人们对其了解甚少。G 蛋白门控内向整流 K+(GIRK 或 Kir3)通道介导由 G 蛋白偶联受体(GPCR)诱发的突触后抑制,GPCR 通过抑制性 G 蛋白发出信号。依赖于 GIRK 的信号传导受 G 蛋白信号调节蛋白 RGS6 和 RGS7 的调节,但它们在特定神经元中对不同 GPCR-GIRK 信号传导途径的选择性尚不清楚。我们比较了 RGS6 和 RGS7 如何影响海马神经元中 GABAB 受体(GABABR)、5HT1A 受体(5HT1AR)和 A1 腺苷受体(A1R)对 GIRK 通道的调控。我们的数据表明,RGS6 和 RGS7 对 GABABR 和 5HT1AR-GIRK 信号转导和区隔化做出了非冗余的贡献,并表明 GPCR-G 蛋白的偏好和 RGS 蛋白的底物偏向,以及 Gαo 参与和效应物进入的受体依赖性差异,塑造了海马神经元中 GPCR-GIRK 信号转导的动态。
{"title":"Receptor-dependent influence of R7 RGS proteins on neuronal GIRK channel signaling dynamics","authors":"Haichang Luo ,&nbsp;Allison Anderson ,&nbsp;Ikuo Masuho ,&nbsp;Ezequiel Marron Fernandez de Velasco ,&nbsp;Lutz Birnbaumer ,&nbsp;Kirill A. Martemyanov ,&nbsp;Kevin Wickman","doi":"10.1016/j.pneurobio.2024.102686","DOIUrl":"10.1016/j.pneurobio.2024.102686","url":null,"abstract":"<div><div>Most neurons are influenced by multiple neuromodulatory inputs that converge on common effectors. Mechanisms that route these signals are key to selective neuromodulation but are poorly understood. G protein-gated inwardly rectifying K<sup>+</sup> (GIRK or Kir3) channels mediate postsynaptic inhibition evoked by G protein-coupled receptors (GPCRs) that signal via inhibitory G proteins. GIRK-dependent signaling is modulated by Regulator of G protein Signaling proteins RGS6 and RGS7, but their selectivity for distinct GPCR-GIRK signaling pathways in defined neurons is unclear. We compared how RGS6 and RGS7 impact GIRK channel regulation by the GABA<sub>B</sub> receptor (GABA<sub>B</sub>R), 5HT<sub>1A</sub> receptor (5HT<sub>1A</sub>R), and A<sub>1</sub> adenosine receptor (A<sub>1</sub>R) in hippocampal neurons. Our data show that RGS6 and RGS7 make non-redundant contributions to GABA<sub>B</sub>R- and 5HT<sub>1A</sub>R-GIRK signaling and compartmentalization and suggest that GPCR-G protein preferences and the substrate bias of RGS proteins, as well as receptor-dependent differences in Gα<sub>o</sub> engagement and effector access, shape GPCR-GIRK signaling dynamics in hippocampal neurons.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"243 ","pages":"Article 102686"},"PeriodicalIF":6.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
CB1 receptors in NG2 cells mediate cannabinoid-evoked functional myelin regeneration NG2 细胞中的 CB1 受体可介导由 CANNABINOID 引起的功能性髓鞘再生。
IF 6.7 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-11-09 DOI: 10.1016/j.pneurobio.2024.102683
Aníbal Sánchez de la Torre , Sara Ezquerro-Herce , Alba Huerga-Gómez , Ester Sánchez-Martín , Juan Carlos Chara , Carlos Matute , Krisztina Monory , Susana Mato , Beat Lutz , Manuel Guzmán , Tania Aguado , Javier Palazuelos
Defects in myelin homeostasis have been reported in many neuropathological conditions. Cannabinoid compounds have been shown to efficiently promote myelin regeneration in animal models of demyelination. However, it is still unknown whether this action relies mostly on a cell autonomous effect on oligodendroglial-lineage-NG2 cells. By using conditional genetic mouse models, here we found that cannabinoid CB1 receptors located on NG2 cells are required for oligodendroglial differentiation and myelin regeneration after demyelination. Selective CB1 receptor gene depletion in NG2 cells following toxin-induced demyelination disrupted oligodendrocyte regeneration and functional remyelination and exacerbated axonal damage. These deficits were rescued by pharmacological blockade of the RhoA/ROCK/Cofilin pathway. Conversely, tetrahydrocannabinol administration promoted oligodendrocyte regeneration and functional remyelination in wild-type but not Ng2-CB1-deficient mice. Overall, this study identifies CB1 receptors as essential modulators of remyelination and support the therapeutic potential of cannabinoids for promoting remyelination in neurological disorders.
据报道,许多神经病理学疾病都存在髓鞘稳态缺陷。研究表明,在脱髓鞘动物模型中,大麻素化合物能有效促进髓鞘再生。然而,这种作用是否主要依赖于对少突胶质细胞-髓鞘-NG2细胞的细胞自主效应仍不得而知。通过使用条件性遗传小鼠模型,我们在此发现位于 NG2 细胞上的大麻素 CB1 受体是脱髓鞘后少突胶质细胞分化和髓鞘再生所必需的。在毒素诱导的脱髓鞘后,NG2 细胞上的选择性 CB1 受体基因耗竭会破坏少突胶质细胞再生和功能性再髓鞘化,并加剧轴突损伤。通过药物阻断 RhoA/ROCK/Cofilin 通路,这些缺陷得到了挽救。相反,服用四氢大麻酚能促进野生型小鼠的少突胶质细胞再生和功能性髓鞘再形成,但不能促进 Ng2-CB1 基因缺陷小鼠的再生和功能性髓鞘再形成。总之,这项研究确定了 CB1 受体是再髓鞘化的重要调节剂,并支持大麻素促进神经系统疾病再髓鞘化的治疗潜力。
{"title":"CB1 receptors in NG2 cells mediate cannabinoid-evoked functional myelin regeneration","authors":"Aníbal Sánchez de la Torre ,&nbsp;Sara Ezquerro-Herce ,&nbsp;Alba Huerga-Gómez ,&nbsp;Ester Sánchez-Martín ,&nbsp;Juan Carlos Chara ,&nbsp;Carlos Matute ,&nbsp;Krisztina Monory ,&nbsp;Susana Mato ,&nbsp;Beat Lutz ,&nbsp;Manuel Guzmán ,&nbsp;Tania Aguado ,&nbsp;Javier Palazuelos","doi":"10.1016/j.pneurobio.2024.102683","DOIUrl":"10.1016/j.pneurobio.2024.102683","url":null,"abstract":"<div><div>Defects in myelin homeostasis have been reported in many neuropathological conditions. Cannabinoid compounds have been shown to efficiently promote myelin regeneration in animal models of demyelination. However, it is still unknown whether this action relies mostly on a cell autonomous effect on oligodendroglial-lineage-NG2 cells. By using conditional genetic mouse models, here we found that cannabinoid CB<sub>1</sub> receptors located on NG2 cells are required for oligodendroglial differentiation and myelin regeneration after demyelination. Selective CB<sub>1</sub> receptor gene depletion in NG2 cells following toxin-induced demyelination disrupted oligodendrocyte regeneration and functional remyelination and exacerbated axonal damage. These deficits were rescued by pharmacological blockade of the RhoA/ROCK/Cofilin pathway. Conversely, tetrahydrocannabinol administration promoted oligodendrocyte regeneration and functional remyelination in wild-type but not <em>Ng2</em>-CB<sub>1</sub>-deficient mice. Overall, this study identifies CB<sub>1</sub> receptors as essential modulators of remyelination and support the therapeutic potential of cannabinoids for promoting remyelination in neurological disorders.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"243 ","pages":"Article 102683"},"PeriodicalIF":6.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Opposing effects of nicotine on hypothalamic arcuate nucleus POMC and NPY neurons 尼古丁对下丘脑弓状核 POMC 和 NPY 神经元的相反作用
IF 6.7 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-11-01 DOI: 10.1016/j.pneurobio.2024.102682
E. Ramírez-Sánchez, A. Mondragón-García, J. Garduño, F. Hernández-Vázquez, S. Ortega-Tinoco, S. Hernández-López
The hypothalamic arcuate nucleus (ARC) contains two main populations of neurons essential for energy homeostasis: neuropeptide Y (NPY) neurons, which are orexigenic and stimulate food intake, and proopiomelanocortin (POMC) neurons, which have an anorexigenic effect. Located near the blood-brain barrier, ARC neurons sense blood-borne signals such as leptin, insulin, and glucose. Exogenous substances, such as nicotine, can also alter ARC neuron activity and energy balance. Nicotine, an addictive drug used worldwide, inhibits appetite, and reduces body weight, although its mechanisms in regulating ARC neurons are not well understood. Using electrophysiological techniques in brain slices, we investigated the effects of nicotine on POMC and NPY neurons at physiological glucose concentrations. We found that nicotine increased the firing rate of POMC and inhibited NPY neurons. Additionally, nicotine-enhanced glutamatergic inputs to POMC cells and GABAergic inputs to NPY neurons, mediated by α7 and α4β2 nicotinic acetylcholine receptors (nAChRs), respectively. These findings can contribute to the understanding of the anorexigenic effects of nicotine in smokers.
下丘脑弓状核(ARC)包含对能量平衡至关重要的两大类神经元:神经肽 Y(NPY)神经元和原绒毛膜促皮质素(POMC)神经元,前者具有促食欲作用,后者具有厌食作用。ARC 神经元位于血脑屏障附近,能感知瘦素、胰岛素和葡萄糖等血源性信号。尼古丁等外源性物质也会改变 ARC 神经元的活动和能量平衡。尼古丁是一种全球通用的成瘾性药物,可抑制食欲并减轻体重,但其调节 ARC 神经元的机制尚不十分清楚。我们利用脑片电生理技术,研究了尼古丁在生理葡萄糖浓度下对 POMC 和 NPY 神经元的影响。我们发现,尼古丁能提高 POMC 的发射率并抑制 NPY 神经元。此外,尼古丁还分别通过α7和α4β2烟碱乙酰胆碱受体(nAChRs)介导,增强了POMC细胞的谷氨酸能输入和NPY神经元的GABA能输入。这些发现有助于了解尼古丁对吸烟者的厌食效应。
{"title":"Opposing effects of nicotine on hypothalamic arcuate nucleus POMC and NPY neurons","authors":"E. Ramírez-Sánchez,&nbsp;A. Mondragón-García,&nbsp;J. Garduño,&nbsp;F. Hernández-Vázquez,&nbsp;S. Ortega-Tinoco,&nbsp;S. Hernández-López","doi":"10.1016/j.pneurobio.2024.102682","DOIUrl":"10.1016/j.pneurobio.2024.102682","url":null,"abstract":"<div><div>The hypothalamic arcuate nucleus (ARC) contains two main populations of neurons essential for energy homeostasis: neuropeptide Y (NPY) neurons, which are orexigenic and stimulate food intake, and proopiomelanocortin (POMC) neurons, which have an anorexigenic effect. Located near the blood-brain barrier, ARC neurons sense blood-borne signals such as leptin, insulin, and glucose. Exogenous substances, such as nicotine, can also alter ARC neuron activity and energy balance. Nicotine, an addictive drug used worldwide, inhibits appetite, and reduces body weight, although its mechanisms in regulating ARC neurons are not well understood. Using electrophysiological techniques in brain slices, we investigated the effects of nicotine on POMC and NPY neurons at physiological glucose concentrations. We found that nicotine increased the firing rate of POMC and inhibited NPY neurons. Additionally, nicotine-enhanced glutamatergic inputs to POMC cells and GABAergic inputs to NPY neurons, mediated by α7 and α4β2 nicotinic acetylcholine receptors (nAChRs), respectively. These findings can contribute to the understanding of the anorexigenic effects of nicotine in smokers.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"242 ","pages":"Article 102682"},"PeriodicalIF":6.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Alterations of synaptic plasticity in Angelman syndrome model mice are rescued by 5-HT7R stimulation 安杰尔曼综合征模型小鼠突触可塑性的改变可通过 5-HT7R 刺激得到缓解。
IF 6.7 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-11-01 DOI: 10.1016/j.pneurobio.2024.102684
Amelia Pizzella , Eduardo Penna , Yan Liu , Natalia Abate , Enza Lacivita , Marcello Leopoldo , Carla Perrone-Capano , Marianna Crispino , Michel Baudry , Xiaoning Bi
Angelman syndrome (AS) is a severe neurodevelopmental disorder characterized by motor disfunction, seizures, intellectual disability, speech deficits, and autism-like behavior, showing high comorbidity with Autism Spectrum Disorders (ASD). It is known that stimulation of the serotonin receptor 7 (5-HT7R) can rescue some of the behavioral and neuroplasticity dysfunctions in animal models of Fragile X and Rett syndrome, two pathologies associated with ASD. In view of these observations, we hypothesised that alterations of 5-HT7R signalling might also be involved in AS. To test this hypothesis, we stimulated 5-HT7R with the selective agonist LP-211 to investigate its possible beneficial effects on synaptic dysfunctions and altered behavior in the AS mice model. In mutant mice, we observed impairment of the synaptic machinery of protein synthesis, which was reversed by 5-HT7R activation. Moreover, stimulation of 5-HT7R was able to: i) enhance dendritic spine density in hippocampal neurons, which was reduced in AS mice; ii) restore impaired long-term potentiation (LTP) in hippocampal slices of the AS mice; iii) improve cognitive performance of the mutant animals subjected to the fear conditioning paradigm. Altogether, our results, showing beneficial effects of 5-HT7R stimulation in restoring molecular and cognitive deficits associated with AS, suggest that targeting 5-HT7R could be a promising therapeutic approach for the pathology.
安杰尔曼综合征(AS)是一种严重的神经发育障碍,以运动功能障碍、癫痫发作、智力障碍、语言障碍和类似自闭症的行为为特征,与自闭症谱系障碍(ASD)有很高的合并率。众所周知,刺激血清素受体 7(5-HT7R)可以挽救脆性 X 和雷特综合征(与 ASD 相关的两种病症)动物模型的一些行为和神经可塑性功能障碍。鉴于这些观察结果,我们假设 5-HT7R 信号的改变也可能与 AS 有关。为了验证这一假设,我们用选择性激动剂 LP-211 刺激 5-HT7R,研究其对 AS 小鼠模型中突触功能障碍和行为改变可能产生的有益影响。在突变小鼠中,我们观察到蛋白质合成的突触机制受损,而 5-HT7R 的激活可逆转这种情况。此外,刺激 5-HT7R 还能:i) 增强 AS 小鼠海马神经元树突棘密度(AS 小鼠的树突棘密度降低);ii) 恢复 AS 小鼠海马切片受损的长期电位(LTP);iii) 改善突变动物在恐惧条件反射范式下的认知能力。总之,我们的研究结果表明,刺激5-HT7R对恢复强直性脊柱炎相关的分子和认知缺陷有益,这表明以5-HT7R为靶点可能是治疗该病症的一种很有前景的方法。
{"title":"Alterations of synaptic plasticity in Angelman syndrome model mice are rescued by 5-HT7R stimulation","authors":"Amelia Pizzella ,&nbsp;Eduardo Penna ,&nbsp;Yan Liu ,&nbsp;Natalia Abate ,&nbsp;Enza Lacivita ,&nbsp;Marcello Leopoldo ,&nbsp;Carla Perrone-Capano ,&nbsp;Marianna Crispino ,&nbsp;Michel Baudry ,&nbsp;Xiaoning Bi","doi":"10.1016/j.pneurobio.2024.102684","DOIUrl":"10.1016/j.pneurobio.2024.102684","url":null,"abstract":"<div><div>Angelman syndrome (AS) is a severe neurodevelopmental disorder characterized by motor disfunction, seizures, intellectual disability, speech deficits, and autism-like behavior, showing high comorbidity with Autism Spectrum Disorders (ASD). It is known that stimulation of the serotonin receptor 7 (5-HT7R) can rescue some of the behavioral and neuroplasticity dysfunctions in animal models of Fragile X and Rett syndrome, two pathologies associated with ASD. In view of these observations, we hypothesised that alterations of 5-HT7R signalling might also be involved in AS. To test this hypothesis, we stimulated 5-HT7R with the selective agonist LP-211 to investigate its possible beneficial effects on synaptic dysfunctions and altered behavior in the AS mice model. In mutant mice, we observed impairment of the synaptic machinery of protein synthesis, which was reversed by 5-HT7R activation. Moreover, stimulation of 5-HT7R was able to: i) enhance dendritic spine density in hippocampal neurons, which was reduced in AS mice; ii) restore impaired long-term potentiation (LTP) in hippocampal slices of the AS mice; iii) improve cognitive performance of the mutant animals subjected to the fear conditioning paradigm. Altogether, our results, showing beneficial effects of 5-HT7R stimulation in restoring molecular and cognitive deficits associated with AS, suggest that targeting 5-HT7R could be a promising therapeutic approach for the pathology.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"242 ","pages":"Article 102684"},"PeriodicalIF":6.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Progress in Neurobiology
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