Optimization of a Minimally-Invasive Bidirectional Optogenetic Peripheral Nerve Interface with Single Axon Read-in & Read-out Specificity

项目摘要 我们建议开发一种长期可植入的、全光学的光遗传神经接口， 侵入性地、光学地神经调节副交感神经或周围神经中的神经的单个轴突 系统拟议的接口将有利于治疗人类疾病和残疾有关的 由颈迷走神经支配的胸部和腹部器官和系统，如癫痫， 代谢紊乱。我们建议将这些神经中的传入/传出轴突与 目的是调节受其支配的器官或大脑回路。双向光学神经接口 该技术将利用光遗传学的能力， 和/或传出神经元与遗传靶向的、光学活化的报道蛋白和视蛋白的结合。 我们的中心前提是，我们可以使用光学与神经轴突沟通。用于光学 我们需要将动作电位转化为光信号。这可以通过使用 遗传编码的钙指示剂或其他电压敏感蛋白， 在神经元中产生动作电位的特性。因为神经并不自然地表达视觉信号 蛋白质，我们将与表达这些蛋白质的转基因小鼠合作，并使用这些小鼠模型来完善 我们的系统，然后再提供给其他研究人员使用。 我们的目标是开发一种紧凑的台式光学系统，可以与其他研究实验室共享， 能够询问神经内特定的神经束和轴突的独特能力。未来这个 这项技术具有转化为人类临床应用的潜力。提案中的技术是 雄心勃勃，但我们已经形成了一个优秀的团队，细胞生物学家，神经科学家，生物医学，电气， 机械工程师。该团队在多个领域的成功合作方面有着出色的记录。 赠款和出版物。

Project Abstract We propose to develop a chronically implantable, all optical, optogenetic nerve interface that can non- invasively, optically neuromodulate individual axons of nerves in the parasympathetic or peripheral nervous system. The proposed interface would benefit treatment of human disease and disabilities related to the thoracic and abdominal organs and systems innervated by the cervical vagus nerve, such as epilepsy and metabolic disorders. We propose to optically interface from afferent/efferent axons in these nerves with the goal of modulating organs or brain circuits innervated by them. The bidirectional optical neural interface technology will utilize the capabilities of optogenetics enabled through viral vector transfection of afferent and/or efferent neurons with genetically targeted, optically activated reporter proteins and opsins. Our central premise is that we can use optics to communicate with axons in a nerve. For optical approaches to work we need to convert action potentials into an optical signal. This can be done using genetically encoded calcium indicators or other voltage sensitive proteins that change their fluorescent properties upon action potential generation in a neuron. Because nerves do not naturally express optical proteins, we will work with transgenic mice that express these proteins and use these mice models to refine our system before making it available for other researchers to use. We aim to develop a compact, bench-top optical system that can be shared with other research labs to provide the unique ability of being able to interrogate specific fascicles and axons within the nerve. In the future, this technology has potential for translation to human clinical applications. The technology in the proposal is ambitious, but we have formed an outstanding team of cell biologists, neuroscientists, biomedical, electrical, and mechanical engineers. The team has an excellent track record of successful collaborations on multiple grants and publications.