Enhanced Optogenetic Control of Neuronal Activity with Tailored Light Stimuli

通过定制光刺激增强神经元活动的光遗传学控制

• 批准号: 1403660
• 负责人: Stephen Boppart
• 金额: $ 45万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1403660&HistoricalAwards=false
• 关键词: Enhanced; Optogenetic; Control; Neuronal; Activity

Proposal Number: 1403660P.I.: Boppart, Stephen A. Title: Enhanced Optogenetic Control of Neuronal Activity with Tailored Light StimuliNon-Technical ExplanationSignificance:This project will investigate how new forms of light may enhance the electrical output and control of neurons that have been genetically modified to be light-sensitive. Optogenetics is a rapidly developing field that uses molecular biology techniques to enable cellular functions to be controlled with light. When neurons (nerve cells) are genetically modified to express a light-activated membrane channel, they can be made to trigger electrical activity when exposed to light. This new level of light-activated control over neuronal activity has yet to be fully exploited, but is offering new opportunities for understanding how neurons and their electrical circuits function within the brain to form thoughts, memories, behaviors, and emotions. In optical science and engineering, advances now make it possible to generate a wide range of new forms of light with customized properties, or what is called tailored light. This research is highly significant and important for the fields of neuroscience and biophotonics. Biophotonics is the science of how light interacts with biological cells and tissues, and neuroscientists seek to understand how the brain and mind work. The new optical sources for generating tailored light in this project will change the way in which we use optogenetics to investigate and understand the function of neurons, neural circuits, and the brain. This project is also highly interdisciplinary, and will provide a unique educational and training opportunity for undergraduate and graduate students to help them solve the complex interdisciplinary problems in engineering and biology in the future. Results from this research will also be integrated into undergraduate and graduate courses in biophotonics, neuroscience, and advanced microscopy. The long-term societal benefits of this research will include raising the public's scientific literacy of how neurons and neural circuits in our brain function, and how new types of light and lasers can be used to probe the complex functions of our brain.Technical DescriptionOptogenetics is a rapidly expanding field, and one that originated out of the field of neuroscience, where genetic modifications to mammalian neurons enabled photo-activated control of membrane channels to elicit action potentials. While this concept has provided a unique toolkit for exploring neuroscience questions and envisioning new medical science applications, there have been relatively few advances or contributions to optogenetics from the fields of optical science and engineering. This proposal addresses this gap by using advanced optical sources and precise control over the optical properties of the light stimuli to enhance the neural control in optogenetics.The innovation of this research project is the ability to generate new forms of tailored light, and apply this light as new forms of stimuli to excite, modulate, and control the output of optogenetically-modified neurons in new ways. Conceivably, it is much more practical to modify and control the light stimulus than to genetically modify the biological properties of cells and tissues. As optogenetics advances to in vivo applications, this practical advantage will be even more significant. Therefore, our hypothesis is that by precisely controlling the spectral, temporal, and spatial parameters of novel tailored light stimuli, it is possible to provide enhanced modulation and control of the electrical output activity of optogenetically-modified neurons. To prove our hypothesis, our research plan will be guided by three objectives. First, we will construct an optical stimulus and microscope system to generate these new forms of tailored light. Second, we will optically stimulate and electrically/optically record from cultured hippocampal neurons that have been genetically modified to express Channelrhodopsin-2, a light-gated membrane ion channel, to investigate how tailored light stimuli alters the electrical output and activity from these cells. Third, we will implement an optical feedback system that will measure the optical response of the neurons and adjust the light stimuli parameters to optimize, modulate, and control the electrical output.The successful outcome of this research project will have far-reaching impact in not only the field of biophotonics, but also in neuroscience and optical science and engineering. Just as optogenetics is expected to make a broad impact in neuroscience, as well as medical science, this research will potentially have an even greater and more rapid impact because it will conceivably be more practical to tailor the light stimulus than to modify the biology to enhance the optogenetic control in the future.This award is being made jointly by two Programs- (1) Biophotonics, in the Division of Chemical, Bioengineering, Environmental and Transport Systems (Engineering Directorate), and (2) Instrument Development for Biological Research, in the Division of Biological Infrastructure (Biological Sciences Directorate).

提案编号：1403660p.i。：Boppart，StephenA。标题：使用量身定制的光刺激性刺激性解释的神经元活性增强了光遗传学控制：该项目将研究新形式的光线如何增强对遗传改性的神经元的电气输出和控制，从而如何增强光敏感的神经元。 光遗传学是一个快速发展的领域，它使用分子生物学技术来使细胞功能得到光控制。 当对神经元（神经细胞）进行遗传修饰以表达光激活的膜通道时，可以在暴露于光线时触发电活动。 这种对神经元活动的新型光激活控制尚未得到充分利用，但是为了解神经元及其电路在大脑中如何发挥作用以形成思想，记忆，行为和情感的新机会。 在光学科学和工程学中，进步现在可以生成具有定制特性或所谓的量身定制光线的各种新形式的光线。 这项研究对于神经科学和生物素化学领域非常重要，而且很重要。 生物探测是光的科学，即光如何与生物细胞和组织相互作用，而神经科学家则试图了解大脑和心理的工作方式。 在该项目中生成量身定制光的新光源将改变我们使用光遗传学研究和了解神经元，神经回路和大脑功能的方式。 该项目也是高度跨学科的，它将为本科和研究生提供独特的教育和培训机会，以帮助他们在将来解决工程和生物学中复杂的跨学科问题。 这项研究的结果还将纳入生物素，神经科学和晚期显微镜的本科和研究生课程。 这项研究的长期社会益处将包括提高公众对神经元和神经回路如何在我们的大脑功能中的科学素养，以及如何使用新型的光和激光器来探测我们大脑的复杂功能。技术描述末期遗传学是快速扩展的领域，以及一种源自植物学的领域，是一种神经控制的领域，是一种神经系统的领域，粘液式粘液效率 - 膜通道引起动作潜力。 尽管这个概念为探索神经科学问题和设想新的医学应用程序提供了独特的工具包，但来自光学科学和工程领域的光遗传学的进步或贡献相对较少。 This proposal addresses this gap by using advanced optical sources and precise control over the optical properties of the light stimuli to enhance the neural control in optogenetics.The innovation of this research project is the ability to generate new forms of tailored light, and apply this light as new forms of stimuli to excite, modulate, and control the output of optogenetically-modified neurons in new ways. 可以想象，修改和控制光刺激比基因修改细胞和组织的生物学特性要实用得多。 随着光遗传学在体内应用中的发展，这种实际优势将更加重要。 因此，我们的假设是，通过精确控制新型量身定制的光刺激的光谱，时间和空间参数，可以提供增强的调制和控制光遗传学改性神经元的电输出活性。 为了证明我们的假设，我们的研究计划将由三个目标指导。 首先，我们将构建一个光刺激和显微镜系统，以生成这些新形式的量身定制光。 其次，我们将从遗传修饰的海马神经元中进行光学刺激并进行电/光学记录，这些神经元已经过遗传修饰，以表达光门控膜离子通道（一种光门控膜离子通道），以研究量身定制的光刺激如何改变这些细胞的电输出和活性。 第三，我们将实施一个光学反馈系统，该系统将测量神经元的光学响应，并调整光刺激参数以优化，调节和控制电气输出。该研究项目的成功结果不仅对生物植物学领域产生深远的影响，而且在神经科学和光学科学和光学科学和工程学方面也会产生深远的影响。 正如预计上遗传学对神经科学以及医学科学产生广泛的影响一样，这项研究可能会产生更大和更快的影响，因为可以想象，量身定制光刺激比修改生物学以增强未来的光源控制更加实用。局）和（2）生物学研究的仪器开发（生物科学局）。