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Brainstem Circuits Controlling Action Diversification. 控制动作多样化的脑干回路。
IF 13.9 1区 医学 Q1 NEUROSCIENCES Pub Date : 2019-07-08 DOI: 10.1146/annurev-neuro-070918-050201
Ludwig Ruder, Silvia Arber

Neuronal circuits that regulate movement are distributed throughout the nervous system. The brainstem is an important interface between upper motor centers involved in action planning and circuits in the spinal cord ultimately leading to execution of body movements. Here we focus on recent work using genetic and viral entry points to reveal the identity of functionally dedicated and frequently spatially intermingled brainstem populations essential for action diversification, a general principle conserved throughout evolution. Brainstem circuits with distinct organization and function control skilled forelimb behavior, orofacial movements, and locomotion. They convey regulatory parameters to motor output structures and collaborate in the construction of complex natural motor behaviors. Functionally tuned brainstem neurons for different actions serve as important integrators of synaptic inputs from upstream centers, including the basal ganglia and cortex, to regulate and modulate behavioral function in different contexts.

调节运动的神经回路分布在整个神经系统。脑干是上部运动中枢(参与行动计划)和脊髓回路(最终导致身体运动的执行)之间的重要接口。在这里,我们关注最近的工作,利用遗传和病毒入口点来揭示功能专用和经常空间混合的脑干群体的身份,这对行动多样化至关重要,这是整个进化过程中保守的一般原则。具有独特组织和功能的脑干回路控制熟练的前肢行为、口面部运动和运动。它们将调节参数传递给运动输出结构,并在复杂的自然运动行为的构建中合作。不同行为的功能调节脑干神经元作为来自上游中枢(包括基底神经节和皮层)的突触输入的重要整合者,在不同环境下调节和调节行为功能。
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引用次数: 41
The Emerging Nature of Astrocyte Diversity. 星形胶质细胞多样性的新兴性质。
IF 13.9 1区 医学 Q1 NEUROSCIENCES Pub Date : 2019-07-08 DOI: 10.1146/annurev-neuro-070918-050443
Baljit S Khakh, Benjamin Deneen

Astrocytes are morphologically complex, ubiquitous cells that are viewed as a homogeneous population tiling the entire central nervous system (CNS). However, this view has been challenged in the last few years with the availability of RNA sequencing, immunohistochemistry, electron microscopy, morphological reconstruction, and imaging data. These studies suggest that astrocytes represent a diverse population of cells and that they display brain area- and disease-specific properties and functions. In this review, we summarize these observations, emphasize areas where clear conclusions can be made, and discuss potential unifying themes. We also identify knowledge gaps that need to be addressed in order to exploit astrocyte diversity as a biological phenomenon of physiological relevance in the CNS. We thus provide a summary and a perspective on astrocyte diversity in the vertebrate CNS.

星形胶质细胞是一种形态复杂、普遍存在的细胞,被视为遍布整个中枢神经系统(CNS)的同质细胞群。然而,在过去的几年里,随着RNA测序、免疫组织化学、电子显微镜、形态重建和成像数据的可用性,这种观点受到了挑战。这些研究表明星形胶质细胞代表了不同的细胞群,它们显示出大脑区域和疾病特异性的特性和功能。在这篇综述中,我们总结了这些观察结果,强调了可以得出明确结论的领域,并讨论了潜在的统一主题。我们还确定了需要解决的知识空白,以便利用星形细胞多样性作为中枢神经系统生理相关的生物现象。因此,我们对脊椎动物中枢神经系统中星形胶质细胞的多样性进行了总结和展望。
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引用次数: 276
What, If, and When to Move: Basal Ganglia Circuits and Self-Paced Action Initiation. 什么,如果和何时运动:基底神经节回路和自定节奏动作启动。
IF 13.9 1区 医学 Q1 NEUROSCIENCES Pub Date : 2019-07-08 Epub Date: 2019-04-24 DOI: 10.1146/annurev-neuro-072116-031033
Andreas Klaus, Joaquim Alves da Silva, Rui M Costa

Deciding what to do and when to move is vital to our survival. Clinical and fundamental studies have identified basal ganglia circuits as critical for this process. The main input nucleus of the basal ganglia, the striatum, receives inputs from frontal, sensory, and motor cortices and interconnected thalamic areas that provide information about potential goals, context, and actions and directly or indirectly modulates basal ganglia outputs. The striatum also receives dopaminergic inputs that can signal reward prediction errors and also behavioral transitions and movement initiation. Here we review studies and models of how direct and indirect pathways can modulate basal ganglia outputs to facilitate movement initiation, and we discuss the role of cortical and dopaminergic inputs to the striatum in determining what to do and if and when to do it. Complex but exciting scenarios emerge that shed new light on how basal ganglia circuits modulate self-paced movement initiation.

决定做什么,什么时候搬家对我们的生存至关重要。临床和基础研究已经确定基底神经节回路对这一过程至关重要。基底神经节的主要输入核纹状体接收来自额叶皮质、感觉皮质和运动皮质以及相互连接的丘脑区域的输入,这些输入提供有关潜在目标、背景和行动的信息,并直接或间接地调节基底神经节的输出。纹状体也接受多巴胺能输入,它可以发出奖励预测错误的信号,也可以发出行为转变和运动启动的信号。在这里,我们回顾了直接和间接通路如何调节基底神经节输出以促进运动启动的研究和模型,并讨论了皮层和多巴胺能输入纹状体在决定做什么以及是否和何时做什么的作用。复杂但令人兴奋的场景出现,揭示了基底神经节回路如何调节自节奏运动的开始。
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引用次数: 157
Early Binaural Hearing: The Comparison of Temporal Differences at the Two Ears. 早期双耳听力:双耳时间差异的比较。
IF 13.9 1区 医学 Q1 NEUROSCIENCES Pub Date : 2019-07-08 Epub Date: 2019-04-24 DOI: 10.1146/annurev-neuro-080317-061925
Philip X Joris, Marcel van der Heijden

Many mammals, including humans, are exquisitely sensitive to tiny time differences between sounds at the two ears. These interaural time differences are an important source of information for sound detection, for sound localization in space, and for environmental awareness. Two brainstem circuits are involved in the initial temporal comparisons between the ears, centered on the medial and lateral superior olive. Cells in these nuclei, as well as their afferents, display a large number of striking physiological and anatomical specializations to enable submillisecond sensitivity. As such, they provide an important model system to study temporal processing in the central nervous system. We review the progress that has been made in characterizing these primary binaural circuits as well as the variety of mechanisms that have been proposed to underlie their function.

许多哺乳动物,包括人类,对两只耳朵声音之间的微小时间差非常敏感。这些内部时间差异是声音探测、空间声音定位和环境意识的重要信息来源。两个脑干回路参与了两耳间最初的时间比较,以橄榄上内侧和外侧为中心。这些细胞核中的细胞,以及它们的传入神经,显示出大量惊人的生理和解剖特化,以实现亚毫秒级的灵敏度。因此,它们为研究中枢神经系统的时间加工提供了一个重要的模型系统。我们回顾了在表征这些主要双耳回路以及各种机制方面所取得的进展,这些机制已被提出以支持其功能。
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引用次数: 26
Peeling the Onion of Brain Representations. 剥开大脑表征的洋葱。
IF 13.9 1区 医学 Q1 NEUROSCIENCES Pub Date : 2019-07-08 DOI: 10.1146/annurev-neuro-080317-061906
Nikolaus Kriegeskorte, Jörn Diedrichsen

The brain's function is to enable adaptive behavior in the world. To this end, the brain processes information about the world. The concept of representation links the information processed by the brain back to the world and enables us to understand what the brain does at a functional level. The appeal of making the connection between brain activity and what it represents has been irresistible to neuroscience, despite the fact that representational interpretations pose several challenges: We must define which aspects of brain activity matter, how the code works, and how it supports computations that contribute to adaptive behavior. It has been suggested that we might drop representational language altogether and seek to understand the brain, more simply, as a dynamical system. In this review, we argue that the concept of representation provides a useful link between dynamics and computational function and ask which aspects of brain activity should be analyzed to achieve a representational understanding. We peel the onion of brain representations in search of the layers (the aspects of brain activity) that matter to computation. The article provides an introduction to the motivation and mathematics of representational models, a critical discussion of their assumptions and limitations, and a preview of future directions in this area.

大脑的功能是使世界上的适应性行为得以实现。为此,大脑处理有关世界的信息。表征的概念将大脑处理的信息与世界联系起来,使我们能够在功能层面上理解大脑的活动。在大脑活动和它所代表的东西之间建立联系的吸引力对神经科学来说是不可抗拒的,尽管表征性解释提出了几个挑战:我们必须定义大脑活动的哪些方面是重要的,代码是如何工作的,以及它如何支持有助于适应行为的计算。有人建议,我们可以完全放弃表征性语言,更简单地把大脑理解为一个动态系统。在这篇综述中,我们认为表征的概念在动力学和计算功能之间提供了有用的联系,并提出应该分析大脑活动的哪些方面来实现表征性理解。我们剥开大脑表象的洋葱,寻找与计算有关的层次(大脑活动的各个方面)。本文介绍了表征模型的动机和数学,对其假设和局限性进行了批判性讨论,并对该领域的未来方向进行了预览。
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引用次数: 84
Neuronal Development of Hearing and Language: Cochlear Implants and Critical Periods. 听力和语言的神经元发育:人工耳蜗和关键期。
IF 13.9 1区 医学 Q1 NEUROSCIENCES Pub Date : 2019-07-08 Epub Date: 2019-01-30 DOI: 10.1146/annurev-neuro-080317-061513
Andrej Kral, Michael F Dorman, Blake S Wilson

The modern cochlear implant (CI) is the most successful neural prosthesis developed to date. CIs provide hearing to the profoundly hearing impaired and allow the acquisition of spoken language in children born deaf. Results from studies enabled by the CI have provided new insights into (a) minimal representations at the periphery for speech reception, (b) brain mechanisms for decoding speech presented in quiet and in acoustically adverse conditions, (c) the developmental neuroscience of language and hearing, and (d) the mechanisms and time courses of intramodal and cross-modal plasticity. Additionally, the results have underscored the interconnectedness of brain functions and the importance of top-down processes in perception and learning. The findings are described in this review with emphasis on the developing brain and the acquisition of hearing and spoken language.

现代人工耳蜗(CI)是迄今为止最成功的神经假体。ci为重度听障者提供听力,并使先天失聪的儿童能够习得口语。CI支持的研究结果为以下方面提供了新的见解:(a)语音接收外围的最小表征,(b)在安静和声学不利条件下解码语音的大脑机制,(c)语言和听力的发育神经科学,以及(d)模态内和跨模态可塑性的机制和时间过程。此外,这些结果强调了大脑功能的相互联系以及自上而下的过程在感知和学习中的重要性。在这篇综述中,研究结果将重点放在大脑发育和听力和口语的习得上。
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引用次数: 93
Probing Computation in the Primate Visual System at Single-Cone Resolution. 灵长类视觉系统在单锥分辨率下的探测计算。
IF 13.9 1区 医学 Q1 NEUROSCIENCES Pub Date : 2019-07-08 Epub Date: 2019-03-11 DOI: 10.1146/annurev-neuro-070918-050233
A Kling, G D Field, D H Brainard, E J Chichilnisky

Daylight vision begins when light activates cone photoreceptors in the retina, creating spatial patterns of neural activity. These cone signals are then combined and processed in downstream neural circuits, ultimately producing visual perception. Recent technical advances have made it possible to deliver visual stimuli to the retina that probe this processing by the visual system at its elementary resolution of individual cones. Physiological recordings from nonhuman primate retinas reveal the spatial organization of cone signals in retinal ganglion cells, including how signals from cones of different types are combined to support both spatial and color vision. Psychophysical experiments with human subjects characterize the visual sensations evoked by stimulating a single cone, including the perception of color. Future combined physiological and psychophysical experiments focusing on probing the elementary visual inputs are likely to clarify how neural processing generates our perception of the visual world.

当光线激活视网膜上的锥状光感受器,产生神经活动的空间模式时,日光视觉就开始了。然后,这些锥体信号在下游神经回路中进行组合和处理,最终产生视觉感知。最近的技术进步使得向视网膜传递视觉刺激成为可能,这种刺激可以以单个视锥细胞的基本分辨率探测视觉系统的这一处理过程。来自非人灵长类视网膜的生理记录揭示了视网膜神经节细胞中锥体信号的空间组织,包括来自不同类型锥体的信号如何组合以支持空间和颜色视觉。对人类受试者进行的心理物理实验描述了刺激单个锥体所引起的视觉感觉,包括对颜色的感知。未来结合生理和心理物理的实验,聚焦于探索基本的视觉输入,可能会澄清神经处理如何产生我们对视觉世界的感知。
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引用次数: 16
Pathophysiology and Mechanisms of Zika Virus Infection in the Nervous System. 寨卡病毒感染神经系统的病理生理学和机制。
IF 13.9 1区 医学 Q1 NEUROSCIENCES Pub Date : 2019-07-08 DOI: 10.1146/annurev-neuro-080317-062231
Kimberly M Christian, Hongjun Song, Guo-Li Ming

In 2015, public awareness of Zika virus (ZIKV) rose in response to alarming statistics of infants with microcephaly being born to women who were infected with the virus during pregnancy, triggering global concern over these potentially devastating consequences. Although we have discovered a great deal about the genome and pathogenesis of this reemergent flavivirus since this recent outbreak, we still have much more to learn, including the nature of the virus-host interactions and mechanisms that determine its tropism and pathogenicity in the nervous system, which are in turn shaped by the continual evolution of the virus. Inevitably, we will find out more about the potential long-term effects of ZIKV exposure on the nervous system from ongoing longitudinal studies. Integrating clinical and epidemiological data with a wider range of animal and human cell culture models will be critical to understanding the pathogenetic mechanisms and developing more specific antiviral compounds and vaccines.

2015 年,由于怀孕期间感染寨卡病毒的妇女所生的婴儿出现小头畸形的惊人数据,公众对寨卡病毒(ZIKV)的认识有所提高,引发了全球对这些潜在破坏性后果的关注。尽管自最近的疫情爆发以来,我们已经发现了大量有关这种重新出现的黄病毒的基因组和致病机理的信息,但我们仍有许多东西需要了解,包括病毒与宿主相互作用的性质以及决定其在神经系统中的滋养和致病性的机制,而这些又是由病毒的不断进化所决定的。不可避免的是,我们将从正在进行的纵向研究中进一步了解 ZIKV 暴露对神经系统的潜在长期影响。将临床和流行病学数据与更广泛的动物和人类细胞培养模型相结合,对于了解致病机制和开发更具特异性的抗病毒化合物和疫苗至关重要。
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引用次数: 0
Unified Classification of Molecular, Network, and Endocrine Features of Hypothalamic Neurons. 下丘脑神经元分子、网络和内分泌特征的统一分类。
IF 13.9 1区 医学 Q1 NEUROSCIENCES Pub Date : 2019-07-08 Epub Date: 2019-02-08 DOI: 10.1146/annurev-neuro-070918-050414
Roman A Romanov, Alán Alpár, Tomas Hökfelt, Tibor Harkany

Peripheral endocrine output relies on either direct or feed-forward multi-order command from the hypothalamus. Efficient coding of endocrine responses is made possible by the many neuronal cell types that coexist in intercalated hypothalamic nuclei and communicate through extensive synaptic connectivity. Although general anatomical and neurochemical features of hypothalamic neurons were described during the past decades, they have yet to be reconciled with recently discovered molecular classifiers and neurogenetic function determination. By interrogating magnocellular as well as parvocellular dopamine, GABA, glutamate, and phenotypically mixed neurons, we integrate available information at the molecular, cellular, network, and endocrine output levels to propose a framework for the comprehensive classification of hypothalamic neurons. Simultaneously, we single out putative neuronal subclasses for which future research can fill in existing gaps of knowledge to rationalize cellular diversity through function-determinant molecular marks in the hypothalamus.

外周内分泌输出依赖于来自下丘脑的直接或前馈多阶指令。内分泌反应的有效编码是由多种神经元细胞共存于嵌入的下丘脑核中,并通过广泛的突触连接进行交流而成为可能的。虽然下丘脑神经元的一般解剖和神经化学特征在过去的几十年里被描述,但它们还没有与最近发现的分子分类器和神经遗传功能测定相协调。通过询问大细胞和副细胞多巴胺、GABA、谷氨酸和表型混合神经元,我们整合了分子、细胞、网络和内分泌输出水平的现有信息,提出了一个下丘脑神经元综合分类的框架。同时,我们挑选出假定的神经元亚类,未来的研究可以填补现有的知识空白,通过下丘脑的功能决定分子标记来合理化细胞多样性。
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引用次数: 27
Light-Sheet Microscopy in Neuroscience. 神经科学中的光片显微镜。
IF 12.1 1区 医学 Q1 NEUROSCIENCES Pub Date : 2019-07-08 DOI: 10.1146/annurev-neuro-070918-050357
Elizabeth M C Hillman, Venkatakaushik Voleti, Wenze Li, Hang Yu

Light-sheet microscopy is an imaging approach that offers unique advantages for a diverse range of neuroscience applications. Unlike point-scanning techniques such as confocal and two-photon microscopy, light-sheet microscopes illuminate an entire plane of tissue, while imaging this plane onto a camera. Although early implementations of light sheet were optimized for longitudinal imaging of embryonic development in small specimens, emerging implementations are capable of capturing light-sheet images in freely moving, unconstrained specimens and even the intact in vivo mammalian brain. Meanwhile, the unique photobleaching and signal-to-noise benefits afforded by light-sheet microscopy's parallelized detection deliver the ability to perform volumetric imaging at much higher speeds than can be achieved using point scanning. This review describes the basic principles and evolution of light-sheet microscopy, followed by perspectives on emerging applications and opportunities for both imaging large, cleared, and expanded neural tissues and high-speed, functional imaging in vivo.

光片显微镜是一种成像方法,为神经科学的各种应用提供了独特的优势。与共聚焦显微镜和双光子显微镜等点扫描技术不同,光片显微镜照亮组织的整个平面,同时将该平面成像到相机上。虽然光片显微镜的早期应用是针对小型标本胚胎发育的纵向成像进行优化,但新出现的应用能够捕捉自由移动、不受约束的标本,甚至完整的活体哺乳动物大脑的光片图像。同时,光片显微镜的并行检测具有独特的光漂白和信噪比优势,能够以比点扫描更快的速度进行体积成像。这篇综述介绍了光片显微镜的基本原理和发展历程,随后展望了光片显微镜在大型、清除和扩展神经组织成像以及体内高速功能成像方面的新兴应用和机遇。
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引用次数: 0
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Annual review of neuroscience
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