High-speed, wide field fluorescent imaging of cortex in freely moving animals

自由活动动物皮层的高速、宽视场荧光成像

• 批准号: 7635195
• 负责人: Eugenio Culurciello
• 金额: $ 58.49万
• 依托单位: JOHN B. PIERCE LABORATORY, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7635195
• 关键词: Affect; Anesthetics; Animal Behavior; Animals; Area; Boxing; Brain; Calcium; Chocolate; Collection; Computer software; Computers and Advanced Instrumentation; Conscience; Consumption; Custom; Data; Development; Devices; Discrimination; Dyes; Electrodes; Electronics; Engineering; Environment; Event; Generations; Head; Heating; Image; Imaging Device; Implant; Laboratories; Light; Lighting; Mammals; Maps; Membrane; Methods; Microelectrodes; Microscope; Milk; Mus; Neurons; Noise; Optics; Paralysed; Patients; Pattern; Physiology; Process; Property; RH1691; Rattus; Resolution; Rewards; Robotics; Rodent; Signal Transduction; Somatosensory Cortex; Source; Speed; System; Temperature; Testing; Time; Tissues; Training; Translating; Validation; Vibrissae; Weight; awake; barrel cortex; brain machine interface; calcium green; design; engineering design; fluorescence microscope; improved; in vivo; lens; light intensity; light weight; mind control; miniaturize; novel; olfactory bulb; portability; prototype; public health relevance; release of sequestered calcium ion into cytoplasm; research study; response; restraint; sensor; voltage; whisker discrimination

DESCRIPTION (provided by applicant): The study of neuronal activity in awake, freely moving animals is the most representative view of `normal' neuronal function. Anesthetics and restraint have profound effects on neuronal physiology and the correlate animal behavior. The study of real time neuronal event processing requires recording methods with high temporal bandwidth (>500 kHz) and the ability to detect physiologically relevant events (i.e. voltage changes or calcium flux). Currently only microelectrode recording of single neuronal units, multiunit activity and field potentials have sufficient temporal resolution and portability to allow recording of neuronal activity in freely moving animals. The current project will produce a miniature microscope/imaging chip which can be head mounted and will allow the recording of optical signals of changes in membrane voltage and calcium concentration in neurons in freely moving rodents. We have developed a prototype device that can collect wide field image sequences of fluorescent voltage dye signals. The current application will re-engineer and significantly improve this prototype device. We will systematically engineer each component to maximize excitation light delivery, fluorescent light collection and optical resolution while minimizing weight, volume, and heat generation. The device will be capable of recording rapid (1 kHz) fluorescent image sequences of a 2-3 mm2 area of cortex and detect small changes in F/F (0.1%). The device will contain a custom designed and built excitation light source, dichroic excitation and emission filters, dichroic mirror, collector lens, objective lens and imaging chip. The device will be small (<1.8 cm2) and light weight enough (10g) to be mounted on the head of a freely moving rat and possibly a mouse. The device will be developed and validated in studies of i) barrel cortex activity during active whisking and object discrimination as well as ii) olfactory bulb activity during active sniffing and scent recognition. The device is intended as a precursor to devices that can translate neuronal activity into actions in real time (optical brain machine interface). PUBLIC HEALTH RELEVANCE: This project will develop a device to study brain function in awake, behaving mammals. The device represents the first step in the development of a neuroprosthetic device to capture information from neuronal tissue regarding intended function. Such a device can ultimately be used to allow direct brain control of robotics, computers and instrumentation to allow paralyzed patients a way to exert conscience control of their environment.

描述(申请人提供)：对清醒的、自由活动的动物的神经活动的研究是对正常神经功能的最具代表性的观点。麻醉剂和束缚对神经生理学和相关的动物行为有深远的影响。对实时神经元事件处理的研究需要具有高时间带宽(&gt；500 kHz)的记录方法以及检测生理相关事件(例如，电压变化或钙离子通量)的能力。目前，只有单个神经元单位、多单位活动和场电位的微电极记录具有足够的时间分辨率和便携性，可以记录自由运动动物的神经元活动。目前的项目将生产一种微型显微镜/成像芯片，它可以戴在头上，并允许记录自由活动的啮齿动物神经元中膜电压和钙浓度变化的光学信号。我们研制了一种能够采集大视场荧光电压染料信号序列图像的样机。目前的应用将重新设计并显著改进这一原型设备。我们将对每个组件进行系统设计，以最大限度地提高激发光传输、荧光光收集和光学分辨率，同时将重量、体积和发热量降至最低。该设备将能够记录2-3mm2皮质区域的快速(1 KHz)荧光图像序列，并检测F/F(0.1%)的微小变化。该装置将包括定制设计和建造的激发光源、二向色性激发和发射滤光片、二向色镜、集光镜、物镜和成像芯片。该装置将很小(1.8平方厘米)，重量足够轻(10克)，可以安装在自由移动的老鼠的头上，也可能是老鼠的头上。该设备将被开发并在以下研究中得到验证：i)桶皮质在主动握手和物体识别过程中的活动，以及ii)嗅球在主动嗅觉和气味识别过程中的活动。该设备旨在成为能够将神经元活动实时转化为动作的设备的先驱(光学脑机接口)。与公共健康相关：该项目将开发一种设备来研究清醒、行为正常的哺乳动物的大脑功能。该设备代表了开发神经假体设备的第一步，该设备可以从神经元组织中捕获有关预期功能的信息。这样的设备最终可以用来让大脑直接控制机器人、计算机和仪器，让瘫痪的患者有一种方式对他们的环境进行良心控制。