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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：
9481458
负责人：
RICHARD Fergus ffrench WEIR
金额：
$ 6万
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/9481458
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.

一种能够激活/报告副交感神经轴突活动的光学探针