Inhibitory regulation of neural circuit plasticity in visual cortex

视觉皮层神经回路可塑性的抑制调节

• 批准号: 8594027
• 负责人: Joshua Trachtenberg
• 金额: $ 39.37万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8594027
• 关键词: Accounting; Address; Affect; Amblyopia; Calcium; Cataract; Cells; Depth Perception; Development; Disease; Electrophysiology (science); Etiology; Frequencies; Glutamates; Goals; Image; Interneurons; Kinetics; Label; Laboratories; Lasers; Maps; Measures; Microscopy; Mus; Neurons; Ocular Dominance; Parvalbumins; Photons; Population; Regulation; Research; Resolution; Role; Scanning; Sensory; Somatostatin; Speed; Staging; Strabismus; Synapses; Synaptic Transmission; Techniques; Testing; Time; Vision; Visual; Visual Cortex; Visual system structure; Work; area striata; calcium indicator; critical period; design; early adolescence; excitatory neuron; experience; fluorophore; improved; in vivo; inhibitory neuron; monocular deprivation; multi-photon; neural circuit; novel therapeutics; optogenetics; programs; public health relevance; relating to nervous system; research study; response; therapeutic development; visual performance; visual process; visual processing

ABSTRACT During critical periods of early adolescence, the wiring of circuitry in visual cortex is strongly influenced by sensory experience. Degraded visual experience, as occurs from cataracts or strabismus, during this critical period impairs the development of steopsis and high sptial frequency vision, thereby contributing to the etiology of amblyopia. The long term objectives of this proposal are to understand how sensory experience exerts its influence on cortical circuitry during the critical period, with particular emphasis on the role of inhibitory neurons. To determine how sensory experience acts on inhibitory neurons to gate circuit plasticity we propose three specific aims that leverage state-of-the-art techniques that are already working in our laboratories. To test the hypothesis that altered vision induces a rapid loss of inhibitory responses, which then gates excitatory plasticity, we use 2-photon in vivo imaging to visualize specific types of excitatory and inhibitory neurons in visual cortex of alert mice and then target cell attached patch recordings to these neurons across cortical layers. This approach provides the highest temporal and spatial resolution available. By comparing responses over time, we will reveal the choreography of plasticity across layers. To determine the spatial and temporal kinetics of excitatory/inhibitory network plasticity, we use high-speed 2-photon in vivo microscopy to simultaneously image hundreds of neurons expressing a new, extremely sensitive genetically encoded calcium indicator (GCaMP6). We follow the same populations of neurons before and during ocular dominance plasticity in mice where specific populations of inhibitory neurons are double labeled with a genetically encoded red fluorophore. In the third aim we test the hypothesis that monocular deprivation first changes the synaptic connectivity to fast-spiking interneurons. To do so we use laser scanning glutamate uncaging and channelrhodopsin-assisted circuit mapping. This work will significantly advance our understanding of inhibitory plasticity and address objectives of the Strabismus, Amblyopia, and Visual Processing Program of the NEI to "increase understanding of the critical period in order to determine how experience alters connectivity in the developing visual system"

抽象的 在青春期早期的关键时期，视觉皮层中电路的接线受到强烈的影响 感官体验。在此期间，如白内障或斜视而发生的视觉体验降低了 关键时期会损害Steopsis和高频率视觉的发展，从而有助于 弱视的病因。该提议的长期目标是了解感官 经验在关键时期对皮质回路产生影响，特别是 抑制神经元的作用。确定感官体验如何作用于抑制性神经元到栅极电路 可塑性我们提出了三个利用已经有效的最新技术的特定目标 在我们的实验室。为了测试改变视力的假设会导致抑制反应的快速丧失， 然后，在大门兴奋性可塑性中，我们使用2光片体内成像来可视化特定类型的 警报小鼠的视觉皮层中的兴奋性和抑制性神经元，然后靶细胞连接的斑块记录 这些神经元跨皮质层。这种方法提供了最高的时间和空间分辨率 可用的。通过比较随着时间的推移响应，我们将揭示跨层可塑性的编排。 为了确定兴奋性/抑制网络可塑性的空间和时间动力学，我们使用高速 2光子体内显微镜，同时对数百个表达新的，极度表达的神经元进行图像 敏感的遗传编码钙指标（GCAMP6）。我们遵循相同的神经元种群 在特定抑制性神经元群体的小鼠中，眼前和期间的可塑性之前和期间 用遗传编码的红色荧光团双重标记。在第三个目的中，我们检验了以下假设 单眼剥夺首先将突触连通性改变为快速刺激的中间神经元。为此，我们使用 激光扫描谷氨酸和通道Ropsiss辅助电路映射。这项工作将 显着提高我们对抑制性可塑性的理解，并解决斜视的目标， NEI的弱视和视觉处理程序，以“增加对关键时期的理解 为了确定经验如何改变发展视觉系统的连接”