NCS-FO: Collaborative Research: Rebuilding Neural Pathway Function Using Miniature Integrated Optics for Neuron-Level Readout and Feedback

一种微型可植入装置的开发，允许神经信息从一个大脑区域转移到另一个大脑区域，将对大脑功能的理解产生重大影响，并将适用于脑部疾病的治疗。拟议的研究涵盖神经科学、材料科学、物理和工程，以及will。为学生提供优秀的跨学科研究机会。传播of& # 8232;这项工作将通过教学、额外的教育推广、本科生机会、期刊和会议出版物来进行。这项研究开发出一种光学反馈控制来修复大脑功能的能力将吸引这些未来的科学家。非侵入性反馈控制修复脑功能是神经科学的终极目标之一。遗传编码荧光指示器和光遗传学的最新发展使光学读出和控制成为可能。然而，我们仍然迫切需要了解一个光学反馈系统是如何在清醒行为的动物中完全恢复功能的。这一提议试图首次证明在一个清醒行为的动物中使用工程光学反馈系统的实际功能恢复。该项目将由一个高度跨学科的团队执行，该团队在神经科学、光遗传学和清醒行为动物的认知研究方面拥有广泛的专业知识，同时还有光学和MEMS设备方面的专家。该提案将技术开发方面与具有重大发现潜力的行为研究结合起来。该设备将使大脑功能研究取得前所未有的进展。pi最近开发了一种轻型头戴式微型多光子显微镜技术，可以对脑组织中的数百个神经元进行三维成像。该技术首次将电润湿光学用于激发激光的非机械转向，并实现单细胞分辨率成像。我们建议结合一个空间形状的第二激光，在不同的波长，从我们的激发激光，允许成像和定向光遗传刺激神经元。重要的是，在单个神经元水平上调节神经活动对于控制大脑功能是必不可少的。因此，光学读出和控制具有恢复功能的真正潜力，而不是其他方法，如超声波，脑电图和功能磁共振成像，理论上在空间分辨率上是有限的。我们建议使用实时反馈控制系统来读取和控制梨状皮质中单个神经元的放电。我们将在老鼠身上进行行为研究，以确定当我们有选择地打开和关闭与梨状皮质的输入神经连接时，嗅觉识别与奖励的关联是否可以恢复。梨状皮质被认为是气味识别的代表。这项研究将使我们能够确定哪些神经元包含对决策至关重要的信息。信息传递的振荡基础可以用神经活动的特定频率范围或阶段来测试。这些研究将有助于测试神经回路功能模型，并适用于治疗用途的神经工程设备。

1631912/1631704Gibson/GopinathDevelopment of a miniature implantable device to allow transfer of neural information from one brain area to another will have a major impact on the understanding of brain function and will be applicable to treatment of brain disease. The proposed research spans neuroscience, materials science, physics and engineering, and will
provide excellent interdisciplinary research opportunities for students. Dissemination of
the work will occur through teaching, additional educational outreach, opportunities for undergraduates, and journals and conference publications. The capability of this research to develop an optical feedback control to repair brain function will captivate these future scientists. Non-invasive feedback control to repair brain function is one of the ultimate goals in neuroscience. The recent and evolving development of genetically encoded fluorescent indicators and optogenetics makes optical readout and control a real possibility. However, there is still a critical need to understand how an optical feedback system can fully recover function in an awake behaving animal. This proposal seeks to demonstrate for the first time the actual recovery of function in an awake behaving animal using an engineered optical feedback system. The project will be performed by a highly interdisciplinary team with extensive expertise in neuroscience, optogenetics, and cognitive research in awake behaving animals along with experts in optical and MEMS devices. The proposal combines the technology development side with behavioral research with the potential for major discoveries. Unprecedented progress in the study of brain function will be enabled with the proposed device. The PIs have recently developed technology for a lightweight head-mounted miniature multiphoton microscope that can image over hundreds of neurons in three dimensions in brain tissue. The technology is the first to use electrowetting optics for non-mechanical steering of the excitation laser and enables single cell resolution imaging. We propose to combine a spatially shaped second laser at a different wavelength from our excitation laser to allow both imaging and directed optogenetic stimulation of neurons. Importantly, modulation of neural activity on the level of individual neurons is essential for controlling function in the brain. Therefore readout and control by optics has a real potential to restore function as opposed other methods such as ultrasound, EEG, and fMRI that are theoretically limited in spatial resolution. We propose to readout and control firing of individual neurons in the piriform cortex using a real-time feedback control system. We will use behavior studies in mice to determine if association of olfactory identity with reward can be recovered as we selectively turn on and off the input nerve connections to the piriform cortex where odor identity is thought to be represented. The study will allow us to identify which neurons contain information essential for decision making. The oscillatory basis for information transfer can be tested using certain frequency ranges or phases of neural activity. These studies will be useful for testing models of neural circuit function and applicable for neuroengineering devices for therapeutic use.