Binocular integration in the primate lateral geniculate nucleus

灵长类外侧膝状核中的双眼整合

• 批准号: 9883004
• 负责人: Alexander Vinzenz Maier
• 金额: $ 38.78万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9883004
• 关键词: Address; Affect; Amblyopia; Back; Binocular Vision; Binocular Vision Disorder; Biological Assay; Brain; Cells; Clinical; Communication; Data; Dependence; Diplopia; Disease; Electrophysiology (science); Eye; Feedback; Felis catus; Fire - disasters; Goals; Grant; Human; Intervention; Killer Cells; Knowledge; Lateral Geniculate Body; Location; M cell; Macaca; Measures; Medical; Modeling; Monkeys; Neurons; Outcome; Output; Pathway interactions; Perception; Population; Primates; Process; Property; Psychophysics; Residual state; Retina; Role; Signal Transduction; Stimulus; Strabismus; Structure; Support System; Synapses; Testing; Textbooks; Thalamic structure; Time; Treatment Efficacy; Tweens; Uncertainty; V1 neuron; Vision; Vision Disorders; Visual; Visual Perception; Visual system structure; awake; base; cell type; experience; experimental study; improved; innovation; monocular; multi-electrode arrays; neural circuit; neural model; neuronal circuitry; neurophysiology; novel; optogenetics; response; sensory input; visual processing

PROJECT SUMMARY/ABSTRACT Humans, like all primates, use both eyes in tandem to compute a perceptual interpretation of the visual world. However, binocular vision often fails, causing some of the most common visual disorders such as amblyopia, strabismus, diplopia or stereoblindness. Collectively, binocular visual deficits affect ~10-20% of the population, and the associated problems are generally intractable. Unraveling the neural circuitry that performs binocular integration, which is the goal of the present project, is a critical stepping-stone for developing novel and effec- tive therapeutic approaches. Here, we will fill a pressing gap in our current knowledge about the brain locations and mechanisms that support interocular interactions (cross-talk) between the retinal output of the two eyes. It is still unclear whether the two eyes' signals first meet in the cortex or already interact subcortically. While some data collected in anesthetized cats point to early cross-talk between the two eyes' signals within the tha- lamic relay, other data suggest that this is not the case. The goal of this grant is to resolve the uncertainty be- tween these two alternative possibilities. We will address the question whether there is cross-talk between the two monocular channels before the level of V1 using an innovative, integrative approach that combines simul- taneous multi-electrode array recordings with targeted neuropharmacological and optogenetic interventions. We will answer two fundamental questions. First, we will determine the degree of binocularity of M, P and K neurons in the LGN. We will do so using LGN recordings combined with cell-type specific optogenetics in awake macaques confronted with varying contrast levels during binocular stimulation. As a second step, we will eliminate feedback to the LGN by reversibly inactivating V1. Using laminar arrays, we will determine the residual activity in LGN as well as the current flow in inactivated cortex, which provides a measure of LGN feedforward inputs to V1. The outcome of all experiments combined will conclusively determine the respective roles of primate LGN and V1 for binocular integration, which is of great significance for our general understand- ing of primate vision and associated clinical implications. Without resolving these questions, models of binocu- lar vision will be incomplete or inaccurate, which will hamper medical progress for correcting disorder of bin- ocular vision, such as amblyopia and stereoblindness, which collectively affect one out of every ten people worldwide.

项目概要/摘要 与所有灵长类动物一样，人类同时使用双眼来计算对视觉世界的感知解释。 然而，双眼视觉经常出现故障，导致一些最常见的视觉障碍，例如弱视、 斜视、复视或立体盲。总的来说，双眼视力缺陷影响约 10-20% 的人口， 并且相关的问题通常是难以解决的。解开执行双眼的神经回路 集成是本项目的目标，是开发新颖有效的关键垫脚石 积极的治疗方法。在这里，我们将填补目前关于大脑位置的知识中的一个紧迫空白 以及支持两眼视网膜输出之间的眼间相互作用（串扰）的机制。它 目前尚不清楚两只眼睛的信号是首先在皮质中相遇还是已经在皮质下相互作用。尽管 在麻醉猫身上收集的一些数据表明，猫的两只眼睛的信号之间存在早期串扰。 拉米克继电器，其他数据表明情况并非如此。这笔赠款的目标是解决不确定性问题 介于这两种替代可能性之间。我们将解决之间是否存在串扰的问题 使用创新的综合方法在 V1 水平之前使用两个单眼通道，该方法结合了同步 具有针对性的神经药理学和光遗传学干预的单一多电极阵列记录。 我们将回答两个基本问题。首先，我们将确定M、P和K的双眼度 LGN 中的神经元。我们将使用 LGN 记录结合细胞类型特异性光遗传学来做到这一点 清醒的猕猴在双眼刺激期间面临着不同的对比度水平。作为第二步，我们 将通过可逆地灭活 V1 来消除对 LGN 的反馈。使用层流阵列，我们将确定 LGN 的残余活动以及失活皮层的电流，提供 LGN 的测量 V1 的前馈输入。所有实验的结果结合起来将最终决定各自的 灵长类LGN和V1在双眼整合中的作用，这对于我们的一般理解具有重要意义 灵长类动物的视觉和相关的临床意义。如果不解决这些问题，双目模型 视力将不完整或不准确，这将阻碍纠正视力障碍的医学进步 眼睛视力，例如弱视和立体盲，每十人中就有一人受到影响 全世界。