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Near Infrared Genetically Encoded Voltage Indicators (NIR-GEVIs) for All-Optical Electrophysiology (AOE)

用于全光电生理学 (AOE) 的近红外基因编码电压指示器 (NIR-GEVI)

基本信息

批准号：
9229649
负责人：
SRDJAN D ANTIC
金额：
$ 104.78万
依托单位：
IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE
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：
2016-09-30 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9229649
关键词：
Accelerometer Adverse effects Anions Automobile Driving BRAIN initiative Benchmarking Biological Biological Models Blindness Brain Calcium Cations Cell membrane Cells Cognitive DNA cassette Development Dyes Electrophysiology (science)Electroporation Emerging Technologies Emotional Event Exhibits Face Fluorescence Fluorescence Resonance Energy Transfer Gene Delivery Gene Targeting Genetic Glutamates Goals Image Individual Laboratories Life Light Microelectrodes Molecular Monitor Motor Mus Neurons Neurosciences Opsin Optics Performance Photons Physiology Phytochrome Positioning Attribute Procedures Protein Engineering Proteins Resolution Scanning Series Signal Transduction Slice Staining method Stains System Tail Technology Time Tissue imaging Transgenic Mice Variant Work absorption awake base blind comparative design improved in utero in vivo in vivo imaging instrumentation interest invention light emission mouse model neuronal cell body neuronal circuitry neurotechnology new technology next generation novel optical imaging optogenetics photoacoustic imaging promoter protein structure function quantum recombinase research study sensor small molecule stoichiometry success tool two-photon voltage

项目摘要

Attaining effective optical modulation and readout of neuronal circuit activities has been a longstanding goal in neuroscience and is a key near-term aim of the BRAIN Initiative. Such neurotechnology is required to decipher how the brain’s electrical signals relate to perceptual, cognitive, emotional and motor functions. The idea to use light to modulate neuronal activities found its first broadly successful realization with the development of caged glutamate, but only since the use of genetically encoded (optogenetic) actuators such as channelrhodopsin, has this approach become overwhelmingly successful. The idea to use light to record electrical signals in the brain was conceptualized with the discovery of the first voltage-sensitive dyes more than half a century ago. Voltage imaging approaches have contributed much to our understanding of brain physiology, both at the cellular and systems levels, but the broad experimental use of these small molecule dyes suffers from several limitations including invasive staining procedures, pharmacological side effects, and blindness towards cellular diversity. These three limitations have been overcome by the recent invention of genetically-encoded voltage indicators (GEVIs). Although in many aspects superior to classical voltage sensitive dyes, GEVIs have not yet been satisfactorily optimized and their combination with optogenetic modulation has been difficult to achieve in practice. One major obstacle is the overlap of the spectral bands of light used to activate opsin-based actuators and at the same time excite and image available GEVIs. What is required to overcome this hurdle are well performing far red GEVIs that can be orthogonally combined with blue light-activated opsin-based actuators. We propose to use novel near-infrared (NIR) phytochrome-based fluorescent proteins (FPs) to generate a new class of GEVIs that are excited and fluoresce in the NIR spectrum, building on our expertise to generate GEVIs using GFP-like FPs. We plan to combine these NIR-GEVIs with blue-light activated excitatory and inhibitory opsins, to enable an optical approach that expands classical microelectrode-based intracellular single cell current-clamp recordings to large numbers of genetically defined neurons in awake mice. Transgenic mice in which this tool can be activated via Cre-recombinase expressing driver mouse lines will be one of our key deliverables.

实现有效的光学调制和读出神经元回路活动一直是一个长期的目标