Interrogating Neuronal Membrane Potential Dynamics with Optical Voltage Sensors

用光学电压传感器询问神经元膜电位动态

• 批准号: 10367845
• 负责人: Evan Walker Miller
• 金额: $ 56.21万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10367845
• 关键词: Animal Model; Animals; Behavior; Brain; Cells; Cellular Structures; Chemicals; Color; Complement; Complex; Development; Disease; Electrodes; Electromagnetics; Electron Transport; Emotions; Enzyme Activation; Esthesia; Fluorescence; Genetic; Goals; Health; Human; Image; Kinetics; Ligation; Membrane; Membrane Potentials; Methodology; Methods; Molecular; Monitor; Neurons; Noise; Optical Methods; Optics; Organic Chemistry; Organic Synthesis; Perception; Physiology; Population; Process; Proteins; Reagent; Reporting; Research; Resolution; Signal Transduction; Speed; Synapses; Thick; Thinking; Time; Tissues; Work; absorption; base; design; enzyme substrate; experience; fluorophore; improved; interest; nervous system disorder; novel; relating to nervous system; response; sensor; small molecule; spatiotemporal; tool; two-photon; voltage; voltage sensitive dye

07 Project Summary/Abstract The long-term goal of this project is to interrogate the dynamics of membrane voltage in the context of intact brains with high spatiotemporal resolution. Optical methods to dissect neuronal activity promise to revolutionize our understanding of the brain at the cellular and circuit level; however, our understanding remains incomplete due, in part, to a lack of tools that can report directly on neuronal activity with sufficient speed and sensitivity. We propose to use the power of molecular design and organic chemistry to develop and apply new optical tools for monitoring membrane potential with unprecedented speed and sensitivity in intact brains and without disruptive capacitive load associated with other classes of voltage indicators. We plan to exploit photoinduced electron transfer (PeT) through molecular wires as a versatile platform for optical voltage sensing. We will build a palette of colors for optical voltage sensing that extends into the near infrared regions of the electromagnetic spectrum; we will create new voltage sensors with exceptionally high two-photon absorption cross sections for use in thick tissue and intact brains; and we will explore methods for genetically targeting and localizing ultra- sensitive fluorescent voltage sensors to neurons of interest. Throughout, development of molecular tools will be closely wed to applications in neurons and tissues, and we will apply these tools to understand how membrane potential dynamics change in both healthy and neurological disease states.

07项目摘要/摘要 该项目的长期目标是在完整的背景下审问膜电压的动态 具有高时空分辨率的大脑。剖析神经元活动的光学方法有望革新 我们在细胞和电路水平上对大脑的理解；但是，我们的理解仍然不完整 部分原因是缺乏可以直接以足够速度和灵敏度报告神经元活动的工具。 我们建议利用分子设计和有机化学的力量开发和应用新的光学工具 用于监测膜电位，以完整的大脑和没有前所未有的速度和灵敏度监测 与其他类别的电压指标相关的破坏性电容负载。我们计划利用照片诱导 通过分子电线的电子传输（PET），作为光电传感的多功能平台。我们将建造 颜色的调色板，用于光电压传感，该光线延伸到电磁的近红外区域 光谱;我们将创建新的电压传感器，并具有异常高的两光子吸收横截面 用于厚的组织和完整的大脑；我们将探讨用于遗传靶向和定位超级靶向和定位的方法 敏感的荧光电压传感器对感兴趣的神经元。在整个过程中，分子工具的开发将是 紧密与神经元和组织中的应用密切相关，我们将应用这些工具来了解膜 健康和神经疾病状态的潜在动态变化。