Viral strategies for bi-directional optogenetic control of specific cell types in neocortex of non-transgenic animals

非转基因动物新皮质中特定细胞类型双向光遗传学控制的病毒策略

基本信息

批准号：
10057749
负责人：
David C Lyon
金额：
$ 43.18万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-15 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10057749
关键词：
Afferent Neurons Animal Model Anions Brain region Cations Cells Characteristics Complex Effectiveness Electrophysiology (science)Felis catus Glycoproteins Goals Helper Viruses High Frequency Oscillation Image Individual Infection Injections Ion Channel Gating Lasers Mammals Membrane Potentials Methods Modeling Neocortex Nervous system structure Neural Network (Anatomic)Neurons Opsin Output Pattern Physiologic pulse Play Population Property Proteins Rabies Rabies virus Rattus Reporter Research Role Signal Transduction Stimulus Structure Structure-Activity Relationship System Systems Analysis Techniques Testing Time Training Tva receptor V2 neuron Validation Variant Viral Virus Visual Visual Cortex area striata base cell type design efficacy testing fluorescence imaging in vivo inhibitory neuron light gated millisecond neural network neurophysiology novel novel strategies optical imaging optogenetics presynaptic promoter receptive field red fluorescent protein visual process

项目摘要

Project Summary Here we propose to develop a novel rabies virus based strategy to express two channelrhodopsin proteins independent manipulation of excitatory and inhibitory transmembrane potentials in the same population of neurons. Combined with the use of cell-type specific promoters in helper viruses and rabies pseudotyping, the new suite of viruses will enable full control of excitation and inhibition over specific neural network subtypes of non-transgenic animals. We will apply the new technique here to determine cell type specific contributions of feedforward cortical integration on the emergence of complex visual feature selectivity using highly visual animal models. While our goal is primarily to develop this novel method to study structure-function organization of visual cortex, this technique will be readily applicable to study any brain region. Our proposed technique combines recently available channelrhodopsin cation and anion channel with our recently our developed viral strategies for accessing specific cell types and specific circuits in non- transgenic species (Liu et al., 2013, Curr Biol) opening the door for unprecedented fine scale study of structure-function relationships in highly visual mammals. For this proposal we will apply these new strategies to enable optogenetic manipulation of specific cell types involved in higher order visual cortex receptive field formation. These studies will represent the most direct in vivo assessment of inhibitory neurons and underlying intra- and inter-laminar circuitry of a large, highly visual mammal, advancing our understanding of how basic visual processes arise and depend on complex cortical structure.

项目概要在这里，我们建议开发一种基于狂犬病病毒的新型策略来表达两种视紫红质通道蛋白独立操纵同一群体的兴奋性和抑制性跨膜电位神经元。结合细胞类型特异性启动子在辅助病毒和狂犬病假型分析中的使用，新的病毒套件将能够完全控制特定神经网络亚型的兴奋和抑制非转基因动物。我们将在这里应用新技术来确定细胞类型的特定贡献前馈皮质整合对使用高度视觉的复杂视觉特征选择性的出现动物模型。虽然我们的目标主要是开发这种新方法来研究结构功能组织对于视觉皮层，该技术将很容易适用于研究任何大脑区域。我们提出的技术将最近可用的通道视紫红质阳离子和阴离子通道与我们最近开发了病毒策略，用于访问非特定细胞类型和特定电路转基因物种（Liu et al., 2013, Curr Biol）为前所未有的精细规模研究打开了大门高度视觉哺乳动物的结构与功能关系。对于这个提案，我们将应用这些新策略能够对涉及高阶视觉皮层感受野的特定细胞类型进行光遗传学操作形成。这些研究将代表对抑制性神经元和潜在的最直接的体内评估大型高度视觉哺乳动物的层内和层间电路，增进了我们对基本原理的理解视觉过程的产生并依赖于复杂的皮质结构。