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Amblyopia: New molecular/pharmacological and environmental approaches. 弱视:新的分子/药理学和环境方法。
IF 1.9 4区 医学 Q3 Neuroscience Pub Date : 2018-01-01 DOI: 10.1017/S0952523817000256
Michael P Stryker, Siegrid Löwel

Emerging technologies are now giving us unprecedented access to manipulate brain circuits, shedding new light on treatments for amblyopia. This research is identifying key circuit elements that control brain plasticity and highlight potential therapeutic targets to promote rewiring in the visual system during and beyond early life. Here, we explore how such recent advancements may guide future pharmacological, genetic, and behavioral approaches to treat amblyopia. We will discuss how animal research, which allows us to probe and tap into the underlying circuit and synaptic mechanisms, should best be used to guide therapeutic strategies. Uncovering cellular and molecular pathways that can be safely targeted to promote recovery may pave the way for effective new amblyopia treatments across the lifespan.

新兴技术现在让我们前所未有地能够操纵大脑回路,为治疗弱视提供了新的思路。这项研究正在确定控制大脑可塑性的关键电路元件,并强调潜在的治疗目标,以促进早期及以后视觉系统的重新布线。在这里,我们将探讨这些最新进展如何指导未来的药理学、遗传学和行为学方法来治疗弱视。我们将讨论如何最好地利用动物研究来指导治疗策略,因为动物研究使我们能够探测和挖掘潜在的回路和突触机制。揭示可以安全地靶向促进恢复的细胞和分子途径可能为在整个生命周期中有效的新弱视治疗铺平道路。
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引用次数: 1
Amblyopia: The clinician's view. 弱视:临床医生的观点。
IF 1.9 4区 医学 Q3 Neuroscience Pub Date : 2018-01-01 DOI: 10.1017/S0952523817000189
David Hunter
During the summer of 2015, the Lasker/IRRF Initiative on Amblyopia convened two groups of scientists and clinicians with diverse backgrounds and expertise. The objective was to focus on a problem that seriously affects vision, and to see if new thinking and ideas might be helpful in the understanding of amblyopia and how these ideas can be applied to advance the field. At these sessions, David Hunter described what is currently known about this complex condition and identified the research and clinical challenges that persist. A summary of his presentation serves as an introduction to this report. As a practicing pediatric ophthalmologist, I continue to be frustrated by how frequently I encounter children with amblyopia when it is too late to restore normal or near-normal function. In this introduction to the Lasker/IRRF Initiative’s report Amblyopia: Challenges and Opportunities, I will provide the basics of amblyopia from a clinician’s view to provide common ground that facilitate open-ended discussions among clinicians and researchers interested in improving our understanding of this disease. I will present the current clinical definition of amblyopia and how we make the diagnosis, review what is understood about the cause and the nature of the deficit, provide an overview of current approaches to screening for the disease as well as its treatment, and place amblyopia in the context of its burden to the society. The current clinical definition of amblyopia is best provided by the American Academy of Ophthalmology’s Preferred Practice Pattern on Amblyopia (AAO Pediatric Ophthalmology/Strabismus Panel, 2012).
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引用次数: 2
Novel method using 3-dimensional segmentation in spectral domain-optical coherence tomography imaging in the chick reveals defocus-induced regional and time-sensitive asymmetries in the choroidal thickness—ADDENDUM 在鸡的光谱域光学相干断层成像中使用三维分割的新方法揭示了离焦引起的脉络膜厚度的区域和时间敏感不对称性
IF 1.9 4区 医学 Q3 Neuroscience Pub Date : 2017-11-16 DOI: 10.1017/s0952523817000323
Diane Nava, B. Antony, Li Zhang, M. Abràmoff, C. Wildsoet
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引用次数: 0
Random spatial patterning of cone bipolar cell mosaics in the mouse retina 小鼠视网膜锥体双极细胞嵌合的随机空间模式
IF 1.9 4区 医学 Q3 Neuroscience Pub Date : 2017-01-09 DOI: 10.1017/S0952523816000183
P. Keeley, Jason J Kim, Sammy C. S. Lee, S. Haverkamp, B. Reese
Abstract Retinal bipolar cells spread their dendritic arbors to tile the retinal surface, extending them to the tips of the dendritic fields of their homotypic neighbors, minimizing dendritic overlap. Such uniform nonredundant dendritic coverage of these populations would suggest a degree of spatial order in the properties of their somal distributions, yet few studies have examined the patterning in retinal bipolar cell mosaics. The present study examined the organization of two types of cone bipolar cells in the mouse retina, the Type 2 cells and the Type 4 cells, and compared their spatial statistical properties with those of the horizontal cells and the cholinergic amacrine cells, as well as to random simulations of cells matched in density and constrained by soma size. The Delauney tessellation of each field was computed, from which nearest neighbor distances and Voronoi domain areas were extracted, permitting a calculation of their respective regularity indexes (RIs). The spatial autocorrelation of the field was also computed, from which the effective radius and packing factor (PF) were determined. Both cone bipolar cell types were found to be less regular and less efficiently packed than either the horizontal cells or cholinergic amacrine cells. Furthermore, while the latter two cell types had RIs and PFs in excess of those for their matched random simulations, the two types of cone bipolar cells had spatial statistical properties comparable to random distributions. An analysis of single labeled cone bipolar cells revealed dendritic arbors frequently skewed to one side of the soma, as would be expected from a randomly distributed population of cells with dendrites that tile. Taken together, these results suggest that, unlike the horizontal cells or cholinergic amacrine cells which minimize proximity to one another, cone bipolar cell types are constrained only by their physical size.
视网膜双极细胞将它们的树突树突树突散布在视网膜表面,将它们延伸到其同型邻居的树突场的尖端,从而最大限度地减少树突重叠。这些人群的这种统一的非冗余树突状覆盖可能表明他们的染色体分布具有一定程度的空间顺序,但很少有研究检查视网膜双极细胞嵌合体的模式。本研究考察了小鼠视网膜中2型和4型两种锥体双极细胞的组织结构,并将其与水平细胞和胆碱能无分泌细胞的空间统计特性进行了比较,并对密度匹配且受体大小限制的细胞进行了随机模拟。计算每个油田的Delauney镶嵌,从中提取最近邻距离和Voronoi域面积,从而计算各自的规则性指数(RIs)。计算了场的空间自相关,确定了有效半径和填充系数。与水平细胞或胆碱能无分泌细胞相比,两种锥型双极细胞类型都不太规则,堆积效率也较低。此外,虽然后两种细胞类型的RIs和PFs超过其匹配的随机模拟,但两种类型的锥双极细胞具有与随机分布相当的空间统计特性。对单个标记的锥体双极细胞的分析显示,树突突经常向体细胞的一侧倾斜,这是随机分布的具有树突的细胞群体所期望的。综上所述,这些结果表明,与水平细胞或胆碱能无分泌细胞不同,它们彼此之间的接近程度最小,锥双极细胞类型仅受其物理尺寸的限制。
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引用次数: 6
Organization of the dorsal lateral geniculate nucleus in the mouse. 小鼠背侧膝状核的组织结构
IF 1.1 4区 医学 Q4 NEUROSCIENCES Pub Date : 2017-01-01 DOI: 10.1017/S0952523817000062
Daniel Kerschensteiner, William Guido

The dorsal lateral geniculate nucleus (dLGN) of the thalamus is the principal conduit for visual information from retina to visual cortex. Viewed initially as a simple relay, recent studies in the mouse reveal far greater complexity in the way input from the retina is combined, transmitted, and processed in dLGN. Here we consider the structural and functional organization of the mouse retinogeniculate pathway by examining the patterns of retinal projections to dLGN and how they converge onto thalamocortical neurons to shape the flow of visual information to visual cortex.

丘脑背侧膝状核(dLGN)是视觉信息从视网膜传递到视觉皮层的主要通道。最初,人们将其视为一个简单的中继器,但最近对小鼠的研究揭示了来自视网膜的输入在 dLGN 中的组合、传输和处理方式要复杂得多。在这里,我们通过研究视网膜投射到 dLGN 的模式,以及它们如何汇聚到丘脑皮层神经元,从而形成流向视觉皮层的视觉信息,来探讨小鼠视网膜原视通路的结构和功能组织。
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引用次数: 0
Thalamocortical processing in vision. 视觉中的丘脑皮质处理。
IF 1.9 4区 医学 Q3 Neuroscience Pub Date : 2017-01-01 DOI: 10.1017/S0952523817000049
Reece Mazade, Jose Manuel Alonso

Visual information reaches the cerebral cortex through a major thalamocortical pathway that connects the lateral geniculate nucleus (LGN) of the thalamus with the primary visual area of the cortex (area V1). In humans, ∼3.4 million afferents from the LGN are distributed within a V1 surface of ∼2400 mm2, an afferent number that is reduced by half in the macaque and by more than two orders of magnitude in the mouse. Thalamocortical afferents are sorted in visual cortex based on the spatial position of their receptive fields to form a map of visual space. The visual resolution within this map is strongly correlated with total number of thalamic afferents that V1 receives and the area available to sort them. The ∼20,000 afferents of the mouse are only sorted by spatial position because they have to cover a large visual field (∼300 deg) within just 4 mm2 of V1 area. By contrast, the ∼500,000 afferents of the cat are also sorted by eye input and light/dark polarity because they cover a smaller visual field (∼200 deg) within a much larger V1 area (∼400 mm2), a sorting principle that is likely to apply also to macaques and humans. The increased precision of thalamic sorting allows building multiple copies of the V1 visual map for left/right eyes and light/dark polarities, which become interlaced to keep neurons representing the same visual point close together. In turn, this interlaced arrangement makes cortical neurons with different preferences for stimulus orientation to rotate around single cortical points forming a pinwheel pattern that allows more efficient processing of objects and visual textures.

视觉信息通过连接丘脑外侧膝状核(LGN)和皮层初级视觉区(V1区)的主要丘脑皮质通路到达大脑皮层。在人类中,来自LGN的约340万个传入信号分布在约2400 mm2的V1表面内,猕猴的传入信号数量减少了一半,小鼠的传入信号数量减少了两个数量级以上。丘脑皮层传入事件在视觉皮层中根据其感受野的空间位置进行分类,形成视觉空间图。这张图中的视觉分辨率与V1接收到的丘脑传入事件总数和可用于分类它们的区域密切相关。小鼠的~ 20,000个传入事件仅按空间位置进行分类,因为它们必须在V1区域的4mm2内覆盖大的视野(~ 300度)。相比之下,猫的~ 500000个传入事件也根据眼睛输入和光/暗极性进行分类,因为它们在更大的V1区域(~ 400 mm2)内覆盖较小的视野(~ 200度),这一分类原则可能也适用于猕猴和人类。丘脑分选精度的提高使得左/右眼和光/暗极性的V1视觉地图可以建立多个副本,它们相互交错,以保持代表同一视觉点的神经元紧密相连。反过来,这种交错的排列使得对刺激方向有不同偏好的皮层神经元围绕单个皮质点旋转,形成一个风车图案,可以更有效地处理物体和视觉纹理。
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引用次数: 26
Visual thalamus, "it's complicated". 视丘脑,“这很复杂”。
IF 1.9 4区 医学 Q3 Neuroscience Pub Date : 2017-01-01 DOI: 10.1017/S0952523817000311
Daniel Kerschensteiner, William Guido
as the review by Morgan describes, connectomic approaches show that there is a method to such madness. Indeed, 3-D serial recon-structions of synaptic circuits reveal previously unrecognized higher-order network organization. One intriguing finding from this approach is that mouse dLGN neurons receive more retinal inputs
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引用次数: 1
A cross-species comparison of corticogeniculate structure and function. 皮质脑结构和功能的跨物种比较
IF 1.9 4区 医学 Q3 Neuroscience Pub Date : 2017-01-01 Epub Date: 2017-11-16 DOI: 10.1017/S095252381700013X
J Michael Hasse, Farran Briggs

The corticogeniculate circuit is an evolutionarily conserved pathway linking the primary visual cortex with the visual thalamus in the feedback direction. While the corticogeniculate circuit is anatomically robust, the impact of corticogeniculate feedback on the visual response properties of visual thalamic neurons is subtle. Accordingly, discovering the function of corticogeniculate feedback in vision has been a particularly challenging task. In this review, the morphology, organization, physiology, and function of corticogeniculate feedback is compared across mammals commonly studied in visual neuroscience: primates, carnivores, rabbits, and rodents. Common structural and organizational motifs are present across species, including the organization of corticogeniculate feedback into parallel processing streams in highly visual mammals.

皮质促发器回路是一条进化保守的通路,在反馈方向上将初级视觉皮层与视觉丘脑连接起来。虽然皮质促发器回路在解剖学上很强大,但皮质促发器反馈对视觉丘脑神经元的视觉反应特性的影响却很微妙。因此,发现皮质基底反馈在视觉中的功能一直是一项特别具有挑战性的任务。在这篇综述中,我们比较了视觉神经科学中常研究的哺乳动物:灵长类、食肉类、兔和啮齿类动物的皮质神经元反馈的形态、组织、生理和功能。不同物种存在共同的结构和组织模式,包括高度视觉化的哺乳动物将皮质感受器反馈组织成并行处理流。
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引用次数: 0
A connectomic approach to the lateral geniculate nucleus. 外侧膝状核的连接组入路。
IF 1.9 4区 医学 Q3 Neuroscience Pub Date : 2017-01-01 DOI: 10.1017/S0952523817000116
Josh L Morgan

Although the core functions and structure of the lateral geniculate nucleus (LGN) are well understood, this core is surrounded by questions about the integration of feedforward and feedback connections, interactions between different channels of information, and how activity dependent development restructures synaptic networks. Our understanding of the organization of the mouse LGN is particularly limited given how important it has become as a model system. Advances in circuit scale electron microscopy (cellular connectomics) have made it possible to reconstruct the synaptic connectivity of hundreds of neurons within in a circuit the size of the mouse LGN. These circuit reconstructions can reveal cell type-to-cell type canonical wiring diagrams as well as the higher order wiring motifs that are only visible in reconstructions of intact networks. Connectomic analysis of the LGN therefore not only can answer longstanding questions about the organization of the visual thalamus but also presents unique opportunities for investigating fundamental properties of mammalian circuit formation.

虽然外侧膝状核(LGN)的核心功能和结构已经被很好地理解,但这个核心仍然被前馈和反馈连接的整合、不同信息通道之间的相互作用以及活动依赖性发展如何重构突触网络等问题所包围。我们对小鼠LGN组织的理解特别有限,因为它已经成为一个重要的模型系统。电路级电子显微镜(细胞连接组学)的进步使得在小鼠LGN大小的电路中重建数百个神经元的突触连接成为可能。这些电路重建可以揭示细胞类型到细胞类型的规范接线图,以及只有在完整网络重建中才能看到的高阶线路基序。因此,对LGN的连接组分析不仅可以回答关于视丘脑组织的长期问题,而且还为研究哺乳动物电路形成的基本特性提供了独特的机会。
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引用次数: 2
An evolving view of retinogeniculate transmission. 不断发展的视网膜传导观点。
IF 1.9 4区 医学 Q3 Neuroscience Pub Date : 2017-01-01 DOI: 10.1017/S0952523817000104
Elizabeth Y Litvina, Chinfei Chen

The thalamocortical (TC) relay neuron of the dorsoLateral Geniculate Nucleus (dLGN) has borne its imprecise label for many decades in spite of strong evidence that its role in visual processing transcends the implied simplicity of the term "relay". The retinogeniculate synapse is the site of communication between a retinal ganglion cell and a TC neuron of the dLGN. Activation of retinal fibers in the optic tract causes reliable, rapid, and robust postsynaptic potentials that drive postsynaptics spikes in a TC neuron. Cortical and subcortical modulatory systems have been known for decades to regulate retinogeniculate transmission. The dynamic properties that the retinogeniculate synapse itself exhibits during and after developmental refinement further enrich the role of the dLGN in the transmission of the retinal signal. Here we consider the structural and functional substrates for retinogeniculate synaptic transmission and plasticity, and reflect on how the complexity of the retinogeniculate synapse imparts a novel dynamic and influential capacity to subcortical processing of visual information.

尽管有确凿证据表明,丘脑皮层(TC)在视觉处理中的作用超越了 "中继 "一词所隐含的简单含义,但数十年来,丘脑皮层(TC)背侧膝状突核(dLGN)的中继神经元一直被贴上这个不准确的标签。视网膜神经元突触是视网膜神经节细胞与 dLGN 的 TC 神经元之间进行交流的场所。视束中的视网膜纤维被激活后会产生可靠、快速和强大的突触后电位,从而驱动 TC 神经元中的突触后尖峰。数十年来,人们已经知道皮层和皮层下调节系统可以调节视网膜神经元的传导。视网膜突触本身在发育完善过程中和之后所表现出的动态特性进一步丰富了 dLGN 在视网膜信号传输中的作用。在此,我们探讨了视网膜发生器突触传递和可塑性的结构和功能基质,并思考视网膜发生器突触的复杂性如何为皮层下的视觉信息处理带来了新的动态和影响能力。
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引用次数: 0
期刊
Visual Neuroscience
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