Imaging at the speed of spikes: An electro-optical multiphoton microscope

以尖峰速度成像：光电多光子显微镜

• 批准号: 10516843
• 负责人: Aaron Michael Kerlin
• 金额: $ 198.62万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10516843
• 关键词: Address; Automobile Driving; Behavior; Behavior Control; Behavioral trial; Brain; Cells; Crystallization; Custom; Development; Devices; Disease; Disease model; Electronics; Engineering; Future; Glutamates; Image; Lasers; Learning; Light; Location; Membrane; Methods; Microscope; Neurons; Neurosciences; Optics; Performance; Physics; Potassium; Process; Reaction Time; Reagent; Scanning; Signal Transduction; Speed; Synapses; Synaptic plasticity; System; Technology; Temperature; Time; Work; base; brain volume; design; flexibility; in vivo; in vivo imaging; lightspeed; millisecond; multidisciplinary; multiphoton microscopy; nanosecond; neuromechanism; novel; optogenetics; prototype; relating to nervous system; sensor; simulation; tool; transmission process; two photon microscopy; two-photon; voltage

Abstract Signals in the brain are transmitted and transformed on a millisecond timescale. The precise timing of activity can carry unique information, correlate perceptual decisions, and powerfully influence synaptic plasticity. Therefore, to understand the circuits that generate behavior and the circuit changes responsible for learning, we must interrogate signaling in vivo at millisecond timescales. Since the advent of two-photon microscopy, these signals have primarily been inferred in vivo through the use of fluorescent indicators with far slower dynamics. Recently, neuroscientists have made impressive gains in developing genetically-encoded indicators of neural activity with millisecond dynamics. However, current two-photon technology limits high-fidelity recording of fast membrane-bound indicators to very few compartments and for relatively little time, representing a major barrier to collecting the simultaneous recordings we need to understand the circuits that control behavior. To overcome this barrier, we propose to leverage the unparalleled speed of light deflection through electro-optical crystals. Recent breakthroughs in electro-optical deflection have enabled large increases in deflection range and nanosecond response times. However, small aperture and temperature gradients in commercial devices still limit the performance of these deflectors. We propose an entirely new deflector design capable of deflecting larger laser beams at high speeds. We will use these new deflectors to develop a microscope capable of random-access multiphoton interrogation of neurons and synapses with sub-microsecond access times. This tool to image synaptic and cellular activity across networks of neurons will provide neuroscientists with critical information on the processes that implement computations in the brain, as well as the disruption of these processes in models of disease.

摘要 大脑中的信号在毫秒级的时间尺度上传输和转换。准确的活动时间可以携带独特的信息，关联感知决策，并强烈影响突触的可塑性。因此，为了理解产生行为的电路和负责学习的电路变化，我们必须在毫秒级询问体内的信号。自从双光子显微镜问世以来，这些信号主要是通过使用动力学慢得多的荧光指示剂在体内推断出来的。最近，神经学家在开发具有毫秒动态的遗传编码神经活动指示器方面取得了令人印象深刻的成果。然而，目前的双光子技术将快速膜结合指示剂的高保真记录限制在非常少的隔室和相对较短的时间内，这是收集同时记录的主要障碍，我们需要了解控制行为的电路。为了克服这一障碍，我们建议利用通过电光晶体的无与伦比的光偏转速度。最近在电光偏转方面的突破使偏转范围和纳秒响应时间大幅增加。然而，商业设备中的小孔径和温度梯度仍然限制了这些偏转器的性能。我们提出了一种全新的偏转器设计，能够在高速下使较大的激光偏转。我们将使用这些新的偏转器来开发一种显微镜，能够以亚微秒的访问时间随机访问多光子询问神经元和突触。这种通过神经元网络对突触和细胞活动进行成像的工具，将为神经科学家提供关于在大脑中执行计算的过程以及在疾病模型中这些过程的中断的关键信息。