A replacement multiphoton microscope for in vivo imaging in rodent models of neur

用于神经啮齿动物模型体内成像的替代多光子显微镜

基本信息

批准号：
7595490
负责人：
Brian J Bacskai
金额：
$ 49.15万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-01 至 2010-03-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Multiphoton microscopy is a powerful technique for high resolution intravital imaging in deep tissue, with particularly exciting results obtained from brain imaging. We have successfully implemented and innovated in vivo brain imaging over the past 10 years, most notably in the study of Alzheimer's disease mouse models. These innovations, however, have extended to other brain imaging applications around the world where we have either directly or indirectly assisted in advancing the applications. Our application of multiphoton microscopy began with the first commercial multiphoton microscope, the Biorad 1024MP, which is still functional in the lab, but antiquated. There is no upgrade path for this instrument: it needs to be replaced. We are proposing to purchase a state-of-the-art multiphoton microscopy system to replace this instrument. The configuration of the microscope platform chosen is optimized for fast and deep in-vivo imaging. Using negative chirp optics to compensate for group velocity dispersion in the optical path, the proposed instrument allows optimized pulse-widths for deep tissue imaging with reduced average power. We have assembled a group of experienced, NIH-funded investigators with applications in a variety of neurological diseases that will take advantage of the capabilities of the instrument in an environment rich in experience and proven success. We have been using multiphoton microscopy to image structure and function in vivo on spatial scales as small as a single spine on an identified dendrite from a single neuron. We have developed approaches to image the pathology associated with Alzheimer's disease, neurons, glia, and the vasculature. We have also been using fluorescence lifetime imaging microscopy (FLIM) for sensitive detection of fluorescence resonance energy transfer (FRET), which can be used to reveal interactions between individual proteins. While FLIM has been largely relegated to in vitro or cell culture measurements, we aim to apply FLIM for quantitative imaging in populations of neurons and glia in vivo. The new microscope will be a vital resource for NIH funded imaging studies in mouse models of neurodegenerative diseases, stroke, and epilepsy. PUBLIC HEALTH RELEVANCE: We propose to replace an old multiphoton microscope with a newer more advanced model. We have been using multiphoton microscopy for 10 years to try to understand the pathophysiology in the brain of living mouse models of neurodegenerative disease, and a new microscope will ensure that we can continue our successful research programs.

描述（由申请人提供）：多光子显微镜是一种用于深层组织高分辨率活体成像的强大技术，从脑成像中获得了特别令人兴奋的结果。过去 10 年，我们成功实施并创新了体内脑成像，尤其是在阿尔茨海默病小鼠模型的研究中。然而，这些创新已经扩展到世界各地的其他脑成像应用，我们直接或间接地协助推进这些应用。我们对多光子显微镜的应用始于第一台商用多光子显微镜 Biorad 1024MP，它在实验室中仍然可以使用，但已经过时了。该仪器没有升级途径：需要更换。我们建议购买最先进的多光子显微镜系统来替换该仪器。所选显微镜平台的配置针对快速、深入的体内成像进行了优化。该仪器使用负线性调频光学器件来补偿光路中的群速度色散，可以在降低平均功率的情况下优化深层组织成像的脉冲宽度。我们聚集了一批经验丰富、由 NIH 资助的研究人员，他们的研究领域涉及各种神经系统疾病，他们将在经验丰富且已取得成功的环境中利用仪器的功能。我们一直在使用多光子显微镜在空间尺度上对体内的结构和功能进行成像，空间尺度小到来自单个神经元的已识别树突上的单个脊柱。我们开发了对与阿尔茨海默病、神经元、神经胶质和脉管系统相关的病理学进行成像的方法。我们还一直在使用荧光寿命成像显微镜 (FLIM) 来灵敏检测荧光共振能量转移 (FRET)，这可用于揭示单个蛋白质之间的相互作用。虽然 FLIM 主要用于体外或细胞培养测量，但我们的目标是应用 FLIM 对体内神经元和神经胶质细胞群进行定量成像。新的显微镜将成为美国国立卫生研究院资助的神经退行性疾病、中风和癫痫小鼠模型成像研究的重要资源。公共健康相关性：我们建议用更新的更先进的型号替换旧的多光子显微镜。十年来，我们一直在使用多光子显微镜来尝试了解神经退行性疾病活体小鼠模型大脑的病理生理学，而新型显微镜将确保我们能够继续我们成功的研究计划。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

An acute functional screen identifies an effective antibody targeting amyloid-β oligomers based on calcium imaging.

急性功能筛选基于钙成像识别出针对淀粉样β寡聚体的有效抗体。

DOI：
发表时间：
2018-03-15
期刊：
影响因子：
4.6
作者：
Wang, Xueying;Kastanenka, Ksenia V;Arbel;Commins, Caitlin;Kuzuya, Akira;Lariviere, Amanda J;Krafft, Grant A;Hefti, Franz;Jerecic, Jasna;Bacskai, Brian J
通讯作者：
Bacskai, Brian J

Therapeutic Strategies to Target Calcium Dysregulation in Alzheimer's Disease.

针对阿尔茨海默病钙失调的治疗策略。