Optogenetic modulation of neuronal and behavioral responses in the primate

灵长类动物神经元和行为反应的光遗传学调节

• 批准号: 8401877
• 负责人: ANNA W. ROE
• 金额: $ 28.6万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8401877
• 关键词: Address; Basic Science; Behavior; Behavioral; Behavioral Assay; Brain; Calculi; Clinical; Cognition; Cognitive; Collaborations; Contrast Sensitivity; Detection; Development; Disabled Persons; Disease; Foundations; Genes; Genetic; Goals; Health; Human; Impairment; Injection of therapeutic agent; Institutes; Knowledge; Lead; Light; Maps; Measures; Mediating; Mental disorders; Methodology; Methods; Molecular; Molecular Target; Monkeys; Neural Inhibition; Neurologic; Neurons; Neurosciences Research; Optics; Pathology; Perception; Photic Stimulation; Population; Prevention; Primates; Prosthesis; Proteins; Psychometrics; Publishing; Reporting; Rodent; Role; Sensory; Site; Solid; Technology; Tissues; Viral; Viral Vector; Virus; Visual Perception; Writing; area striata; awake; base; behavior influence; clinical application; cognitive function; handicapping condition; high risk; imaging modality; improved; innovation; insight; meetings; method development; minimally invasive; nervous system disorder; neural circuit; neuronal patterning; neurophysiology; neuropsychiatry; nonhuman primate; novel strategies; optical imaging; optogenetics; photoactivation; relating to nervous system; response; standard measure; success; tool; visual process; visual processing

DESCRIPTION (provided by applicant): Optogenetics refers to a cutting-edge set of molecular methods that allows for light-based control of targeted neurons in intact brains. These methods have immense potential as a basic research tool to determine the role of specific neuronal populations in healthy and abnormal brain function. In addition, further development of these methods may lead to new types of treatments for neurological and psychiatric disorders, as well as a new class of prostheses for those with sensory impairments. This project is aimed at further developing these methods so that they can achieve their basic research and clinical potential. This proposal introduces key improvements in the molecular methods as well as fundamental improvements in their application to the study of higher-order perceptual and cognitive functions. Critically, the approach of this proposal is minimally invasive and hence, unlike previous methods, causes little to no tissue damage. In addition, the improvements introduced by this proposal allow for more precise targeting of neurons and more potent control of the responses of those neurons. This proposal uses these methods to systematically determine their efficacy at both the neuronal and the behavioral levels. A key innovation of this approach is the development of an "optogenetic window". This window will permit long-term health of the cortex, functional mapping prior to delivery of molecular agents, precise targeting of molecular agents to specific functional sites, and assessment with established optical imaging, electrophysiological, and behavioral methods. This proposal will allow patterns of neuronal modulation (both inhibitory and excitatory) to be related to specific perceptual and behavioral effects. The successful completion of this project will have enormous benefits for basic research into higher-order perceptual and cognitive functions, and will provide a solid foundation for the development of new treatments for the sensory impaired as well as those with psychiatric or neurological disorders. PUBLIC HEALTH RELEVANCE: The long-term goal of this project is to provide insight into the neuronal mechanisms that underlie perception and cognition. This project will provide methods and knowledge that will aid in the treatment and prevention of neurological and psychiatric disorders. These aims are also directly relevant to the development of prostheses for the visually handicapped.

描述（由申请人提供）：光遗传学是指一组尖端的分子方法，该方法允许对完整大脑中靶向神经元的基于光控制。这些方法是确定特定神经元种群在健康和异常脑功能中的作用的基础研究工具的巨大潜力。此外，这些方法的进一步开发可能会导致新型的神经和精神疾病的治疗方法，以及针对患有感官障碍者的新的假体。该项目旨在进一步开发这些方法，以便它们可以实现基础研究和临床潜力。 该提案介绍了分子方法的主要改进，以及它们在研究高阶感知和认知功能研究中的基本改进。至关重要的是，该提案的方法是最小的侵入性，因此，与以前的方法不同，它几乎不会造成组织损害。此外，该提案引入的改进可以更精确地靶向神经元，并更有效地控制这些神经元的反应。该建议使用这些方法系统地确定其在神经元和行为水平上的功效。 这种方法的关键创新是“光遗传窗口”的发展。该窗口将允许皮质的长期健康，在递送分子剂之前的功能映射，精确靶向分子剂到特定功能部位的靶向，并通过既定的光学成像，电生理和行为方法进行评估。该建议将允许神经元调节模式（抑制性和兴奋性）与特定的感知和行为效应有关。该项目的成功完成将为高阶感知和认知功能提供基础研究的巨大好处，并为为感官受损的新疗法以及患有精神病或神经系统疾病的新疗法提供稳固的基础。 公共卫生相关性：该项目的长期目标是洞悉感知和认知基础的神经元机制。该项目将提供方法和知识，以帮助治疗和预防神经系统和精神疾病。这些目标也与视力残障的假肢发展直接相关。