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Sculpting Astrocyte Diversity through Circuits and Transcription. 通过电路和转录雕刻星形细胞多样性。
IF 5.6 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-08-01 DOI: 10.1177/10738584221082620
Yi-Ting Cheng, Junsung Woo, Benjamin Deneen

Astrocytes are the most abundant glial cell in the central nervous system and occupy a wide range of roles that are essential for brain function. Over the past few years, evidence has emerged that astrocytes exhibit cellular and molecular heterogeneity, raising the possibility that subsets of astrocytes are functionally distinct and that transcriptional mechanisms are involved in encoding this prospective diversity. In this review, we focus on three emerging areas of astrocyte biology: region-specific circuit regulation, molecular diversity, and transcriptional regulation. This review highlights our nascent understanding of how molecular diversity is converted to functional diversity of astrocytes through the lens of brain region-specific circuits. We articulate our understanding of how transcriptional mechanisms regulate this diversity and key areas that need further exploration to achieve the overarching goal of a functional taxonomy of astrocytes in the brain.

星形胶质细胞是中枢神经系统中最丰富的胶质细胞,在脑功能中起着广泛的重要作用。在过去的几年中,有证据表明星形胶质细胞表现出细胞和分子的异质性,这提高了星形胶质细胞亚群在功能上不同的可能性,并且转录机制参与了编码这种潜在多样性的过程。在这篇综述中,我们重点介绍了星形细胞生物学的三个新兴领域:区域特异性电路调节、分子多样性和转录调节。这篇综述强调了我们对星形胶质细胞的分子多样性如何通过脑区域特异性回路转化为功能多样性的初步理解。我们阐明了我们对转录机制如何调节这种多样性的理解,以及需要进一步探索的关键领域,以实现大脑星形胶质细胞功能分类的总体目标。
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引用次数: 4
Mechanosensitive Ion Channels, Axonal Growth, and Regeneration. 机械敏感离子通道、轴突生长和再生。
IF 5.6 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-08-01 DOI: 10.1177/10738584221088575
Leann Miles, Jackson Powell, Casey Kozak, Yuanquan Song

Cells sense and respond to mechanical stimuli by converting those stimuli into biological signals, a process known as mechanotransduction. Mechanotransduction is essential in diverse cellular functions, including tissue development, touch sensitivity, pain, and neuronal pathfinding. In the search for key players of mechanotransduction, several families of ion channels were identified as being mechanosensitive and were demonstrated to be activated directly by mechanical forces in both the membrane bilayer and the cytoskeleton. More recently, Piezo ion channels were discovered as a bona fide mechanosensitive ion channel, and its characterization led to a cascade of research that revealed the diverse functions of Piezo proteins and, in particular, their involvement in neuronal repair.

细胞通过将机械刺激转化为生物信号来感知和响应机械刺激,这一过程被称为机械转导。机械转导在多种细胞功能中是必不可少的,包括组织发育、触觉敏感、疼痛和神经元寻路。在寻找机械转导的关键角色时,几个离子通道家族被确定为机械敏感的,并被证明直接被膜双分子层和细胞骨架中的机械力激活。最近,压电离子通道被发现是一种真正的机械敏感离子通道,其特性导致了一系列研究,揭示了压电蛋白的多种功能,特别是它们在神经元修复中的作用。
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引用次数: 3
Perspectives on Neuroscience and Behavior. 神经科学与行为透视。
IF 5.6 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-08-01 DOI: 10.1177/10738584231178683
Schizophrenia (SZ) and bipolar disorder (BPD) have many common clinical features and they have shared polygenetic risks. An improved understanding of the common neurobiological pathways involved would be an important advance. Now, this has been accomplished in an outstanding study where it was found that SZ and BPD have upregulation of miR-124-3p in olfactory epithelium derived neuronal cells and postmortem prefrontal cortex, and that this was associated with shared polygenetic risks of the two disorders. In a mouse model with upregulation of miR-124-3p in the medial prefrontal cortex (mPFC) there was increased GRIA2lacking calcium-permeable AMPA receptors (AMPARs) and the mice had impaired social interaction and increased sensitivity to amphetamine. The increase in GRIA2 lacking calcium-permeable AMPARs increased the post-synaptic conductance of AMPARs and miniature excitatory postsynaptic currents (mESPC) amplitude. The selective antagonism of GRIA2-lacking calcium-permeable AMPARs by Naspm normalized the increased amplitude of mESPCs, and local infusion of Naspm into the mPFC reduced the behavioral deficits in social interaction and amphetamine sensitivity. Adeno-associated virus mediated expression of GRIA2 in mouse prefrontal cortex excitatory neurons reduced the behavioral defects (Namkung and others 2023). This article is an outstanding example of how the focus on neurobiological mechanisms underlying behavioral dimensions can improve our understanding of key biological pathways involved in the pathogenesis of behavioral abnormalities. This in turn provides new opportunities for the development of more efficacious therapeutic interventions.
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引用次数: 0
Influencers in the Somatosensory System: Extrinsic Control of Sensory Neuron Phenotypes. 体感觉系统的影响因素:感觉神经元表型的外在控制。
IF 5.6 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-08-01 DOI: 10.1177/10738584221074350
Joriene C de Nooij

Somatosensory neurons in dorsal root ganglia (DRG) comprise several main subclasses: high threshold nociceptors/thermoceptors, high- and low-threshold mechanoreceptors, and proprioceptors. Recent years have seen an explosion in the identification of molecules that underlie the functional diversity of these sensory modalities. They also have begun to reveal the developmental mechanisms that channel the emergence of this subtype diversity, solidifying the importance of peripheral instructive signals. Somatic sensory neurons collectively serve numerous essential physiological and protective roles, and as such, an increased understanding of the processes that underlie the specialization of these sensory subtypes is not only biologically interesting but also clinically relevant.

背根神经节(DRG)中的体感觉神经元包括几个主要亚类:高阈值伤害感受器/热感受器、高阈值和低阈值机械感受器和本体感受器。近年来,在识别这些感觉模式的功能多样性基础上的分子方面出现了爆炸式增长。他们也开始揭示引导这种亚型多样性出现的发育机制,巩固了外周指导信号的重要性。体细胞感觉神经元共同发挥着许多重要的生理和保护作用,因此,对这些感觉亚型特化的过程的进一步了解不仅在生物学上很有趣,而且在临床上也很重要。
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引用次数: 1
The Importance of Cajal's and Lorente de Nó's Neuroscience to the Birth of Cybernetics. 卡哈尔和洛伦特·德Nó的神经科学对控制论诞生的重要性。
IF 5.6 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-07-05 DOI: 10.1177/10738584231179932
Juan Manuel Espinosa-Sanchez, Alex Gomez-Marin, Fernando de Castro

The beginnings of cybernetics were marked by the publication of two papers in 1943. In the first one, Rosenblueth, Wiener, and Bigelow claimed that purposeful behavior is a circular process controlled by negative feedback. In the second seminal paper, McCulloch and Pitts proposed that neurons are interconnected working as logical operators. Both articles raised human-machine analogies and mathematically formulated cognitive mechanisms. These ideas ignited the interest of von Neumann, who was developing the first stored-program computer. Thus, after a preliminary meeting in 1945, a series of meetings were held between 1946 and 1953. The role of the Spanish neurophysiologist Rafael Lorente de Nó in the beginnings of cybernetics is attested not only by his participation in the core members of these Macy conferences but also for his previous description of reverberating circuits formed by a closed chain of internuncial neurons. This was the first neurobiologic demonstration of a feedback loop. Most researchers considered the central nervous system as a mere reflex organ until then; nevertheless, he demonstrated a self-sustained central activity in the nervous system, supporting the idea of self-regulating mechanisms as a key concept not just in machines but also in the brain.

1943年发表的两篇论文标志着控制论的开端。在第一个理论中,Rosenblueth、Wiener和Bigelow声称,有目的的行为是一个由负反馈控制的循环过程。在第二篇开创性的论文中,麦卡洛克和皮茨提出,神经元是相互连接的,作为逻辑运算符工作。这两篇文章都提出了人机类比和数学表述的认知机制。这些想法引起了冯·诺伊曼的兴趣,他当时正在开发第一台存储程序计算机。因此,在1945年举行初步会议之后,在1946年至1953年期间举行了一系列会议。西班牙神经生理学家Rafael Lorente de Nó在控制论初期的作用不仅体现在他参与了梅西会议的核心成员,还体现在他之前对内部神经元封闭链形成的回响回路的描述上。这是第一个反馈回路的神经生物学论证。在此之前,大多数研究人员认为中枢神经系统仅仅是一个反射器官;然而,他证明了神经系统中自我维持的中枢活动,支持了自我调节机制不仅是机器的关键概念,也是大脑的关键概念。
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引用次数: 0
Long Noncoding RNAs in CNS Myelination and Disease. 长链非编码rna在中枢神经系统髓鞘形成和疾病中的作用。
IF 5.6 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-06-01 DOI: 10.1177/10738584221083919
Jing Zhang, Menglong Guan, Xianyao Zhou, Kalen Berry, Xuelian He, Q Richard Lu

Myelination by oligodendrocytes is crucial for neuronal survival and function, and defects in myelination or failure in myelin repair can lead to axonal degeneration and various neurological diseases. At present, the factors that promote myelination and overcome the remyelination block in demyelinating diseases are poorly defined. Although the roles of protein-coding genes in oligodendrocyte differentiation have been extensively studied, the majority of the mammalian genome is transcribed into noncoding RNAs, and the functions of these molecules in myelination are poorly characterized. Long noncoding RNAs (lncRNAs) regulate transcription at multiple levels, providing spatiotemporal control and robustness for cell type-specific gene expression and physiological functions. lncRNAs have been shown to regulate neural cell-type specification, differentiation, and maintenance of cell identity, and dysregulation of lncRNA function has been shown to contribute to neurological diseases. In this review, we discuss recent advances in our understanding of the functions of lncRNAs in oligodendrocyte development and myelination as well their roles in neurological diseases and brain tumorigenesis. A more systematic characterization of lncRNA functional networks will be instrumental for a better understanding of CNS myelination, myelin disorders, and myelin repair.

少突胶质细胞的髓鞘形成对神经元的存活和功能至关重要,髓鞘形成缺陷或髓鞘修复失败可导致轴突变性和各种神经系统疾病。目前,在脱髓鞘疾病中促进髓鞘形成和克服再髓鞘阻滞的因素还不清楚。尽管蛋白质编码基因在少突胶质细胞分化中的作用已被广泛研究,但大多数哺乳动物基因组被转录成非编码rna,这些分子在髓鞘形成中的功能尚不清楚。长链非编码rna (lncRNAs)在多个水平上调控转录,为细胞类型特异性基因表达和生理功能提供时空控制和鲁棒性。lncRNA已被证明可以调节神经细胞类型的规范、分化和细胞身份的维持,lncRNA功能的失调已被证明与神经系统疾病有关。在这篇综述中,我们讨论了lncrna在少突胶质细胞发育和髓鞘形成中的功能以及它们在神经系统疾病和脑肿瘤发生中的作用的最新进展。更系统地表征lncRNA功能网络将有助于更好地理解中枢神经系统髓鞘形成、髓鞘紊乱和髓鞘修复。
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引用次数: 1
The Neuroscientist Comments. 神经科学家评论。
IF 5.6 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-06-01 DOI: 10.1177/10738584231166316
Touch is an essential component of life, providing rich and detailed information on our environment that begins with activation of mechanosensitive nerve endings innervating the skin. This information is then conveyed to higher brain centers through the dorsal column nuclei of the brainstem. However, in addition to input directly from low-threshold mechanoreceptors, the dorsal column nuclei also receive signals from postsynaptic dorsal column neurons of the spinal cord, which in turn also integrate mechanoreceptor signals. In their recent study, Turecek and others (2022) sought to investigate the contribution of input from these indirect postsynaptic dorsal column neurons to the coding of touch sensation. By recording from neuron subtypes in the gracile nucleus, in combination with optogenetic tagging and antidromic stimulation, the authors showed that neurons projecting to the ventral posterolateral thalamus responded to low-frequency vibration stimuli and featured small excitatory receptive fields with large regions of surround suppression, suggesting that these neurons convey precise spatial information. In contrast, dorsal column nuclei neurons projecting to the inferior colliculus responded to a large range of vibration frequencies but with large receptive fields, indicative of a larger dynamic range but less discriminative spatial resolution. To determine the contribution of both direct (via Aβ low-threshold mechanoreceptor projections that travel through the dorsal column) and indirect (via postsynaptic dorsal column neurons of the spinal cord) inputs to the responses of dorsal column nuclei neurons, optogenetic silencing through the light-activated chloride channel was used. These experiments revealed that the indirect pathway contributes in particular to responses to very low-frequency mechanical stimulation (10 Hz) but not low-frequency (50 Hz) or high-frequency (300 Hz) vibration. By pharmacologically blocking neurotransmission of postsynaptic dorsal column neurons in the lumbar dorsal horn, a contribution of the indirect pathway to coding of sustained mechanical stimulation, specifically lowto high-intensity skin indentation, was unveiled. Thus, the indirect pathway appears critical for detection and encoding of stimulus intensities, likely through both lowand high-threshold mechanoreceptors (including Aδ and C fiber neurons) that do not project via the direct dorsal column pathway. Using light-induced activation of Calca-expressing highthreshold mechanoreceptors in a Calca-FlpE; Rosa26FSFReaChR mouse line, which exclusively signal via the indirect pathway, as well as stimulation of the direct pathway by vibration, the receptive fields of both dorsal column pathways were found to be highly correlated, suggesting reconvergence of input signals in the dorsal column nuclei to enable precise spatial and intensity representation of mechanical stimuli in single, small receptive fields. Overall, these elegant experiments demonstrate the impo
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引用次数: 0
Do Endocannabinoids Cause the Runner's High? Evidence and Open Questions. 内源性大麻素会导致跑步者兴奋吗?证据和开放性问题。
IF 5.6 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-06-01 DOI: 10.1177/10738584211069981
Michael Siebers, Sarah V Biedermann, Johannes Fuss

The runner's high is an ephemeral feeling some humans experience during and after endurance exercise. Recent evidence in mice suggests that a runner's high depends on the release of endocannabinoids (eCBs) during exercise. However, little is known under what circumstances eCBs are released during exercise in humans. This systematic review sampled all data from clinical trials in humans on eCB levels following exercise from the discovery of eCBs until April 20, 2021. PubMed/NCBI, Ovid MEDLINE, and Cochrane library were searched systematically and reviewed following the PRISMA guidelines. From 278 records, 21 met the inclusion criteria. After acute exercise, 14 of 17 studies detected an increase in eCBs. In contrast, after a period of long-term endurance exercise, four articles described a decrease in eCBs. Even though several studies demonstrated an association between eCB levels and features of the runner's high, reliable proof of the involvement of eCBs in the runner's high in humans has not yet been achieved due to methodological hurdles. In this review, we suggest how to advance the study of the influence of eCBs on the beneficial effects of exercise and provide recommendations on how endocannabinoid release is most likely to occur under laboratory conditions.

跑步者的兴奋是一些人在耐力运动期间和之后经历的短暂感觉。最近在老鼠身上的证据表明,跑步者的兴奋感取决于运动过程中内源性大麻素(eCBs)的释放。然而,在人类运动过程中,在什么情况下释放出ecb却知之甚少。本系统综述对从发现eCB到2021年4月20日锻炼后人体临床试验的所有数据进行了抽样。系统检索PubMed/NCBI、Ovid MEDLINE和Cochrane图书馆,并按照PRISMA指南进行审查。从278条记录中,有21条符合纳入标准。急性运动后,17项研究中有14项检测到脑电图增加。相比之下,在一段时间的长期耐力运动后,有四篇文章描述了脑电波的减少。尽管有几项研究表明eCB水平与跑步者兴奋的特征之间存在关联,但由于方法上的障碍,尚未获得可靠的证据证明eCB与人类跑步者兴奋有关。在这篇综述中,我们建议如何推进eCBs对运动有益效果影响的研究,并就实验室条件下内源性大麻素释放最有可能发生的方式提出建议。
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引用次数: 10
Gaetano Perusini: The Forgotten Neuroscientist Behind "Alzheimer's" Disease. 盖塔诺·佩鲁西尼:被遗忘的阿尔茨海默病背后的神经科学家。
IF 5.6 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-06-01 DOI: 10.1177/10738584211059466
Francesco Pellegrini, Mattia Rosso, Duong T Chu

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive and behavioral impairment with social and occupational impacts. This form of dementia is being increasingly studied, and its prevalence is expected to rise in the near future. Gaetano Perusini, a neuroscientist in the Alzheimer's laboratory, has played a major clinical and pathological role in the earlier study of Alzheimer's disease. This article summarizes his role in the discovery of the disease, which should be fairly named Alzheimer-Perusini disease.

阿尔茨海默病(AD)是一种以认知和行为障碍为特征的神经退行性疾病,具有社会和职业影响。这种形式的痴呆症正在得到越来越多的研究,预计其患病率将在不久的将来上升。阿尔茨海默氏症实验室的神经科学家盖塔诺·佩鲁西尼(Gaetano Perusini)在阿尔茨海默氏症的早期研究中发挥了重要的临床和病理作用。这篇文章总结了他在发现这种疾病中的作用,这种疾病应该被公平地命名为阿尔茨海默-佩鲁西尼病。
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引用次数: 2
Information Exchange between Cortical Areas: The Visual System as a Model. 皮质区域间的信息交换:视觉系统模型。
IF 5.6 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-06-01 DOI: 10.1177/10738584211069061
Hang Zeng, Siyi Chen, Gereon R Fink, Ralph Weidner

As nearly all brain functions, perception, motion, and higher-order cognitive functions require coordinated neural information processing within distributed cortical networks. Over the past decades, new theories and techniques emerged that advanced our understanding of how information is transferred between cortical areas. This review surveys critical aspects of interareal information exchange. We begin by examining the brain's structural connectivity, which provides the basic framework for interareal communication. We then illustrate information exchange between cortical areas using the visual system as an example. Next, well-studied and newly proposed theories that may underlie principles of neural communication are reviewed, highlighting recent work that offers new perspectives on interareal information exchange. We finally discuss open questions in the study of the neural mechanisms underlying interareal information exchange.

几乎所有的大脑功能,感知、运动和高阶认知功能都需要在分布式皮质网络中协调神经信息处理。在过去的几十年里,新的理论和技术的出现,提高了我们对信息如何在皮层区域之间传递的理解。本综述调查了区域间信息交流的关键方面。我们从检查大脑的结构连接开始,它为区域间交流提供了基本框架。然后,我们以视觉系统为例说明皮层区域之间的信息交换。接下来,我们将回顾一些已经得到充分研究的新提出的理论,这些理论可能是神经通讯原理的基础,重点介绍最近为区域间信息交换提供新视角的工作。最后,我们讨论了区域间信息交换的神经机制研究中的开放性问题。
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引用次数: 0
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