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: 8927645
• 负责人: Joshua Trachtenberg
• 金额: $ 37.25万
• 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 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8927645
• 关键词: Accounting; Address; Affect; Amblyopia; Calcium; Cataract; Cells; Depth Perception; Development; Disease; Electrophysiology (science); Etiology; Frequencies; Glutamates; Goals; Health; Image; Interneurons; Kinetics; Label; Laboratories; Lasers; Maps; Measures; Microscopy; Mus; Neurons; Ocular Dominance; Parvalbumins; 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; in vivo imaging; inhibitory neuron; monocular deprivation; multi-photon; neural circuit; novel therapeutics; optogenetics; programs; relating to nervous system; research study; response; therapeutic development; two-photon; visual performance; visual process; visual processing

DESCRIPTION (provided by applicant): 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 stereopsis and high spatial 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"

描述（由申请人提供）：在青春期早期的关键时期，视觉皮层中的电路布线受到感官体验的强烈影响。在这个关键时期，白内障或斜视引起的视觉体验退化会损害立体视觉和高空间频率视力的发育，从而导致弱视的病因。该提案的长期目标是了解感官体验如何在关键时期对皮质回路产生影响，特别强调抑制性神经元的作用。为了确定感觉体验如何作用于抑制性神经元以控制电路可塑性，我们提出了三个利用状态的具体目标 我们的实验室已经使用了最先进的技术。为了验证视力改变会导致抑制性反应迅速丧失，从而控制兴奋性可塑性的假设，我们使用 2 光子体内成像来可视化警觉小鼠视觉皮层中特定类型的兴奋性和抑制性神经元，然后对细胞附着的斑块记录进行可视化穿过皮质层的这些神经元。这种方法提供了最高的时间和空间分辨率。通过比较随时间变化的反应，我们将揭示跨层可塑性的编排。为了确定兴奋/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、极其敏感的基因编码钙指示剂（GCaMP6）的神经元进行成像。我们在小鼠眼部优势可塑性之前和期间追踪相同的神经元群，其中特定的抑制性神经元群被基因编码的红色荧光团双重标记。在第三个目标中，我们测试了这样的假设：单眼剥夺首先改变了快速尖峰中间神经元的突触连接。为此，我们使用激光扫描谷氨酸解笼和通道视紫红质辅助电路映射。这项工作将显着增进我们对抑制可塑性的理解，并实现抑制可塑性的目标 NEI 的斜视、弱视和视觉处理项目旨在“增加对关键时期的理解，以确定经验如何改变发育中视觉系统的连接性”