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

单轴突读入的微创双向光遗传学周围神经接口的优化

基本信息

批准号：
10667835
负责人：
JOHN H CALDWELL
金额：
$ 8.42万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-30 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10667835
关键词：
3-Dimensional Abdomen Action Potentials Afferent Neurons Alzheimer&apos s Disease Animals Axon Behavior Behavioral Biomedical Research Brain Breathing Calcium Cardiac Cardiology Cells Cervical Chest Chronic Clinical Collaborations Development Devices Disease Efferent Neurons Electrocardiogram Electrodes Engineering Epilepsy FDA approved Fascicle Future Generations Genetic Vectors Glass Goals Grant Heart Heart Rate Human Image Individual Inflammatory Bowel Diseases Injections Lasers Lung Measurement Mechanics Mental Depression Metabolic Diseases Methods Microscope Miniaturization Monitor Mus Needles Nerve Nerve Tissue Neurons Neurosciences Opsin Optics Organ Parasympathetic Nervous System Pathway interactions Penetration Peripheral Peripheral Nerves Peripheral Nervous System Pharmacologic Substance Pharmacology Physiologic pulse Physiological Polymers Property Proteins Publications Reporter Research Research Personnel Resolution Scanning Signal Transduction Source Specificity System Systems Integration Tail Techniques Technology Testing Transgenic Mice United States National Institutes of Health Vagus nerve structure Veins Viral Viral Vector Virus Work awake base body system calcium indicator clinical application conditioned fear disability flexibility heart function heart imaging human disease implantation in vivo innovation lens miniaturize minimally invasive mouse model multiphoton microscopy neuroregulation new technology novel optogenetics portability prototype relating to nervous system side effect stressor translation to humans two-photon virtual voltage

项目摘要

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.

项目摘要我们建议开发一种可长期植入的全光学光遗传学神经接口，它可以非侵入性地、光学地神经调节副交感神经或周围神经中的单个神经轴突系统。拟议的界面将有利于与相关的人类疾病和残疾的治疗由颈迷走神经支配的胸腹部器官和系统，例如癫痫和代谢紊乱。我们建议将这些神经中的传入/传出轴突与调节器官或受其支配的大脑回路的目标。双向光学神经接口该技术将利用通过病毒载体转染传入神经实现的光遗传学功能和/或具有基因靶向、光激活报告蛋白和视蛋白的传出神经元。我们的核心前提是我们可以使用光学与神经中的轴突进行通信。光学用我们需要将动作电位转换为光信号。这可以使用以下方法完成基因编码的钙指示剂或其他改变其荧光的电压敏感蛋白神经元中动作电位产生的特性。因为神经并不自然地表达视觉蛋白质，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，然后再供其他研究人员使用。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，以提供能够询问神经内特定束和轴突的独特能力。未来，这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，但我们已经组建了一支由细胞生物学家、神经科学家、生物医学、电气、和机械工程师。该团队在多个领域拥有成功合作的良好记录赠款和出版物。