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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