Three Dimensional Holography for Parallel Multi-target Optogenetic Circuit Manipulation

 描述(由申请人提供)：了解神经元之间的交流，谁在与谁交谈，以及他们在说什么语言，对于发现大脑电路是如何影响大脑功能和功能障碍至关重要的。在过去的几十年里，神经科学在记录和成像神经元之间的交流方面取得了指数级的进步。此外，遗传学家最近开发了一种能力，通过表达被称为“视蛋白”的光激活微生物蛋白，用光来操纵神经元。现在，神经学家可以驱动神经回路，以确定它们如何产生感觉、知觉和认知功能。为了充分利用光遗传工具，我们正在开发全息方法，将图案光传递到脑组织，使多个神经元能够同时激活，独立控制定向光的强度和时间 到每一个细胞。在这里，我们建议：(1)表征新开发的光学系统，以确定哪些最适合全息激活技术；(2)实现三维全息光图案；以及(3)与研究光学和生理上不同的NeuRA系统中的电路的神经科学家合作，分发和迭代优化3D全息系统。最终目标是开发一个强大的系统，能够以模仿自然发生的活动的模式操纵神经元。通过这种协作优化获得的见解将被用于我们的行业合作伙伴智能成像创新公司(科罗拉多州丹佛市)开发的商业原型的设计。因此，该系统可以广泛分布在体外和体内的神经回路研究中，以发现神经交流是如何产生感觉、感知、认知和行为的。这种洞察力将提高我们确定治疗神经系统疾病和障碍的有效目标和方法的能力。

 DESCRIPTION (provided by applicant): Understanding communication between neurons, who is talking to whom, and what language they are speaking, is essential for discovering how brain circuits underlie brain function and dysfunction. Over the past decades, Neuroscience has made exponential progress toward recording and imaging communication between neurons. In addition, geneticists have recently developed the capability to manipulate neurons with light through the expression of light-activated microbial proteins called "opsins." Now, neuroscientists can drive neural circuits in order to determine how they give rise to sensation, perception, and cognitive function. In order to take full advantage of "optogenetic" tools, we are developing holographic methods to deliver patterned light into brain tissue, to enable simultaneous activation of multiple neurons, independently controlling the strength and timing of light targeted to each cell. Here, we propose to: (1) characterize newly developed opsins to determine which are best suited for holographic activation techniques; (2) implement holographic light patterns in three-dimensions; and, (3) distribute and iteratively optimize the 3D holography system in collaboration with Neuroscientists studying circuits in optically and physiologically diverse neura systems. The end goal is to develop a robust system, capable of manipulating neurons in patterns that mimic naturally occurring activity. Insights gained through this collaborative optimization will be used to inform the design of the commercial prototype developed by our industry collaborator Intelligent Imaging Innovations, Inc. (Denver, CO). The system can thus be widely distributed for neural circuit investigation, both in-vitro and in-vivo, to discover how neual communication gives rise to sensation, perception, cognition, and behavior. Such insights will improve our ability to identify effective targets and methods for treating neurological diseases and disorders.