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

单轴突读入双向光遗传学微创周围神经接口的开发

基本信息

批准号：
9535582
负责人：
RICHARD Fergus ffrench WEIR
金额：
$ 64.52万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-24 至 2018-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9535582
关键词：
Action Potentials Afferent Neurons Alpha Cell Axon Beta Cell Biological Brain Breeding Caliber Cardiac Cervical Collaborations Coupled Detection Development Diabetes Mellitus Diabetic Autonomic Neuropathy Efferent Neurons Event Fascicle Fiber Optics Fluorescent Dyes Generations Glucagon Goals Head Heart Heart Rate Hormones Human Image Implant In Vitro Individual Insulin Islets of Langerhans Label Langerhans cell Lasers Measures Methods Microscope Microscopy Mus Muscle fasciculation Nerve Neurons Neurosciences Optical Instrument Optical reporter Optics Organ Pancreas Pancreatic Diseases Parasympathetic Nervous System Pathway interactions Peripheral Nerves Peripheral Nervous System Physiological Preparation Proteins Ranvier&apos s Nodes Reporter Reporting Research Research Personnel Scanning Sensory Signal Transduction Site Source Specificity Stimulus System Technology Testing Tissues Transgenic Mice Vagus nerve structure Viral Vector Viscera Work aerobic respiration control protein base bioimaging cholinergic design experience experimental study fluorescence imaging imaging system in vivo instrument insulin secretion islet lens member minimally invasive nerve supply neuroregulation novel optical fiber optical imaging optogenetics pancreatic juice portability protein expression response rhodamine dextran tool two-photon

项目摘要

An Optical Probe capable of Activating/Reporting on axon activity in nerves of parasympathetic nervous system would be a boon to researchers working with the pancreas. We are proposing to develop such a Probe using our background and experience in optogenetics in the peripheral nerve, bio-imaging and compact multiphoton microscope design. Current neuro-modulation approaches for the vagus nerve are generally all or nothing events that cause simultaneous changes in heart rate, for example, along with changes in pancreatic function. We propose to develop a novel compact Optogenetic based Optical Probe capable of optically neuromodulating individual afferent and/or efferent axons within nerves of the parasympathetic, or peripheral, nervous system. We seek to read-in or read-out from these nerves with the goal of modulating organs or brain circuits innervated by them. 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 reporter proteins or by some other means that is ancillary to action potential generation. Because nerves do not naturally express optical proteins, we will work with transgenic mice that express these proteins and use these mice to refine our system before making it available for other researchers to use. We will develop a bench-top Optical instrument that can be shared with other research teams to allow us, and them, to interrogate specific fascicles and axons within mouse, and ultimately human, nerves. Our goal here is the vagus nerve and its innervation of the pancreas. The vagus nerve is one of the main conduits into the parasympathetic nervous system. The ability to interface with this nerve gives one the ability to neuromodulate the viscera in one direction and the brain in the other. We are proposing to couple an optical fiber with an electrowetting lens head to allow remote interrogation the vagus nerve with a bench top (i.e. portable) laser system. Integration of miniature (1mm diameter) scale electrowetting electrically tunable optics with an optical fiber-based imaging system will enable two-photon fluorescence imaging of neuron activity by readout of a fluorescent indicator. We will work with our collaborators in the field of pancreatic research to test, refine and demonstrate our ability to activate/report from in-vitro mouse vagus nerves and to see if we can control and/or sense pancreatic responses in the absence of other responses, such as a change in heart rate, using targeted neuro-modulation of specific axons in the vagus in in-vivo transgenic mice experiments.

能够激活/报告副交感神经轴突活动的光学探针该系统对于从事胰腺研究的研究人员来说将是一个福音。我们建议开发这样一个探针利用我们在周围神经、生物成像和紧凑型光遗传学方面的背景和经验多光子显微镜设计。目前迷走神经的神经调节方法通常是全部或没有任何事件会导致心率同时变化，例如，随着胰腺变化功能。我们建议开发一种新型紧凑型基于光遗传学的光学探针，能够以光学方式副交感神经或外周神经内的神经调节个体传入和/或传出轴突，神经系统。我们寻求从这些神经中读入或读出，以达到调节器官或大脑的目的由它们支配的电路。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。这可以使用记者来完成蛋白质或通过其他方式辅助动作电位的产生。因为神经不天然表达光学蛋白质，我们将与表达这些蛋白质的转基因小鼠合作并使用这些蛋白质老鼠来完善我们的系统，然后再供其他研究人员使用。我们将开发一种可以与其他研究团队共享的台式光学仪器，以便我们，和它们，以询问小鼠以及最终人类神经内的特定束和轴突。我们的目标这是迷走神经及其对胰腺的神经支配。迷走神经是进入神经的主要导管之一副交感神经系统。与该神经交互的能力使人能够向一个方向调节内脏，向另一个方向调节大脑。我们建议耦合光学带有电润湿透镜头的光纤，可以使用台式（即，远程询问迷走神经）便携式）激光系统。集成微型（直径 1mm）电润湿电可调光学器件基于光纤的成像系统将能够通过以下方式对神经元活动进行双光子荧光成像荧光指示剂的读数。我们将与胰腺研究领域的合作者合作，测试、完善和展示我们的研究成果。能够激活/报告体外小鼠迷走神经，并查看我们是否可以控制和/或感知胰腺使用有针对性的神经调节在没有其他反应（例如心率变化）的情况下做出反应体内转基因小鼠实验中迷走神经中特定轴突的变化。