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.

抽象的 大脑中的信号以毫秒为单位进行传输和转换。活动的精确时间可以携带独特的信息，关联感知决策，并有力地影响突触可塑性。因此，为了了解产生行为的电路和负责学习的电路变化，我们必须在毫秒时间尺度上询问体内的信号传导。自从双光子显微镜出现以来，这些信号主要是通过使用动态慢得多的荧光指示剂在体内推断的。最近，神经科学家在开发具有毫秒动态的神经活动基因编码指标方面取得了令人瞩目的成果。然而，当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很少的隔间和相对较短的时间内，这成为收集我们了解控制行为的电路所需的同步记录的主要障碍。为了克服这一障碍，我们建议利用电光晶体无与伦比的光偏转速度。最近在电光偏转方面的突破使得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，能够高速偏转较大的激光束。我们将使用这些新的偏转器开发一种显微镜，能够以亚微秒的访问时间对神经元和突触进行随机访问多光子询问。这种对神经元网络中的突触和细胞活动进行成像的工具将为神经科学家提供有关大脑中实现计算的过程以及疾病模型中这些过程的破坏的关键信息。