Optical probes for controlling cellular function

描述(由申请人提供)：提案的目标是开发和测试用于双光子去神经递质的新光学技术。我们之前研制的笼式神经递质已经被世界各地的许多研究小组广泛使用。我们工作的一个重要特点是我们与著名生理学家建立了长期的合作关系。这些相互作用对有用和重要的笼状化合物的发展至关重要，因为它是定义探针的生物学问题。在这项建议中，我们试图解决用于光化学探测神经元功能的光学化学方法领域的一个重要空白，即完成并行信号过程的同时、多模式光学控制的能力。在之前的资助周期中，我们对发色团进行了新的笼化，这种发色团可以在长波长下几乎完全选择性地光解，同时在短波长下具有基本的光稳定性。我们建议将该探针应用于测试有关锥体细胞中兴奋和抑制信号整合的问题。我们还将继续开发化学探针，研究笼形化合物的非靶标药理作用，并开发具有扩展圆周率电子系统的新型笼形化合物。这项提议的总体目标是开发新的光化学工具，允许对树突信号过程进行双向光学控制。

DESCRIPTION (provided by applicant): The goal of proposal is the development and testing of new optical technology for two- photon uncaging of neurotransmitters. The caged neurotransmitters developed we have previously made have been widely used by many research groups around the world. An important feature of our work is that we have forged long-term collaborative relationships with noted physiologists. These interactions have been vital the development of useful and important caged compounds as it is the biological problems that define the probes. In this proposal we seek to address an important gap in the area of optical chemical methods that are used for photochemical probing of neuronal function, namely, the ability to accomplish simultaneous, multimodal optical control of parallel signaling processes. In the previous grant cycle we made new caging that chromophore that can be photolyzed with almost complete chromatic selectivity at long wavelengths of light, whilst being essential photostable at short wavelengths. We propose to apply this probe to test questions concerning the integration of excitatory and inhibitory signals in pyramidal cells. We will also continue to develop chemical probes looking at off-target pharmacological effects of caged compounds and develop new caged compounds with extended pi electron systems. The overall goal of this proposal is to develop new photochemical tools that allow bidirectional optical control of dendritic signaling processes.