NCS-FO: Collaborative Research: Rebuilding neural pathway function using miniature integrated optics for neuron-level readout and feedback

1631912/1631704吉布森/戈皮纳开发一种微型植入式设备，允许将神经信息从一个大脑区域转移到另一个大脑区域，这将对了解大脑功能产生重大影响，并将适用于脑部疾病的治疗。拟议的研究横跨神经科学、材料科学、物理学和工程学，将为学生提供绝佳的跨学科研究机会。将通过教学、额外的教育宣传、本科生的机会以及期刊和会议出版物来传播这项工作。这项研究开发了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。无创反馈控制修复脑功能是神经科学的终极目标之一。基因编码的荧光指示器和光遗传学的最新和不断发展的发展使光学读出和控制成为现实。然而，仍然迫切需要了解光反馈系统如何在清醒的行为动物中完全恢复功能。这项提案试图首次证明，使用工程光学反馈系统，清醒行为的动物的功能实际恢复了。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认知研究方面拥有广泛的专业知识，以及光学和MEMS设备专家。该提案将技术开发方面与行为研究相结合，并具有重大发现的潜力。该设备将使大脑功能的研究取得前所未有的进步。PI最近开发了一种轻型头盔微型多光子显微镜的技术，可以在脑组织中对数百个神经元进行三维成像。该技术是第一个使用电润湿光学对激励激光进行非机械操纵的技术，并使单细胞分辨率成像成为可能。我们建议将空间形状的秒激光与我们的激发激光在不同的波长组合，以允许对神经元进行成像和定向光遗传刺激。重要的是，神经活动在单个神经元水平上的调节对于控制大脑功能是必不可少的。因此，与理论上受到空间分辨率限制的其他方法，如超声波、EEG和fMRI相比，光学读出和控制具有真正的恢复功能的潜力。我们建议使用实时反馈控制系统来读出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，嗅觉认同与奖励的联系是否可以恢复。梨状皮质被认为代表气味认同。这项研究将使我们能够识别哪些神经元包含决策所必需的信息。可以使用神经活动的特定频率范围或阶段来测试信息传递的振荡基础。这些研究将有助于测试神经回路功能的模型，并适用于治疗用的神经工程设备。

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.