MULTIPHOTON CONFOCAL MICROSCOPY SYSTEM: NEURODEGENATIVE, ALZHEIMER'S DISEASE

该子项目是利用由NIH/NCRR资助的共享仪器赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。列出的机构是用于资助的，不一定是研究者的机构。描述（由申请人提供）：了解神经系统发育和功能需要阐明神经回路的单独组件与其在完整系统中的功能之间的关系。在完整的系统中揭示这些关系已被证明是非常困难的传统方法。然而，多光子共聚焦显微镜的出现，提供了机会，在体内光学成像神经元组织内最小的光损伤。该方法可用于将电极记录靶向特定细胞类型或光学探测所识别细胞类型的活性。神经元活动的光学监测可以使用来自钙敏感染料的荧光变化的测量或神经递质的突触前囊泡释放的遗传表达的传感器来完成。在本提案中，我们计划使用多光子共聚焦显微镜，再加上遗传编码的光学报告分子和其他小的荧光分子，来研究正常成人神经系统中神经活动的连接和作用，以及在发育和疾病状态下突触的形成。这些研究只有使用多光子共聚焦显微镜系统才有可能

This subproject is one of many research subprojects utilizing the resources provided by a Shared Instrumentation Grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the grant, which is not necessarily the institution for the investigator. DESCRIPTION (provided by applicant): Understanding nervous system development and function requires elucidation of the relationships between the separate components of neural circuits and their function in an intact system. Revealing these relationships in intact systems has proven to be extremely difficult with conventional methods. The advent of multiphoton confocal microscopy, however, provides the opportunity for in vivo optical imaging deep within neuronal tissue with minimal photodamage. This method can be used to target electrode recordings to specific cell types or to optically probe the activity of identified cell types. Optical monitoring of neuronal activity can be done using measurements of fluorescent changes from calcium sensitive dyes or genetically expressed sensors of presynaptic vesicular release of neurotransmitter. In the present proposal, we plan to use multiphoton confocal microscopy, coupled with genetically encoded optical reporters and other small fluorescence molecules, to study the connectivity and the role of neural activity in the normal adult nervous system and in the formation of synapses during development and in disease states. These studies are only possible with the use of a multiphoton confocal microscopy system