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神经递质双光子捕获的新光学技术。我们之前开发的笼状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，我们与著名的生理学家建立了长期的合作关系。这些相互作用对于开发有用和重要的笼化化合物至关重要，因为它是定义探针的生物学问题。在本提案中，我们试图解决用于神经元功能光化学探测的光化学方法领域的一个重要空白，即实现并行信号处理的同时，多模态光学控制的能力。在之前的资助周期中，我们制造了新的笼状色团，它可以在长波光下以几乎完全的色选择性进行光解，同时在短波光下具有基本的光稳定性。我们建议应用这种探针来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，研究笼化化合物的脱靶药理作用，并开发具有扩展pi电子系统的新型笼化化合物。本提案的总体目标是开发新的光化学工具，允许树突信号传导过程的双向光学控制。

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.