Optical probes for controlling cellular function

用于控制细胞功能的光学探针

• 批准号: 8845619
• 负责人: Graham Ellis-Davies
• 金额: $ 46.53万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8845619
• 关键词: Address; Adrenergic Agonists; Area; Award; Biological; Brain-Derived Neurotrophic Factor; Buffers; Cell physiology; Chemicals; Color; Daughter; Dendrimers; Dendrites; Development; Distal; Electrons; Engineering; GABA Receptor; Generic Drugs; Glutamates; Goals; Grant; Head; Health; Interneurons; Lasers; Light; Location; Methodology; Methods; MicroRNAs; Microscopy; Monitor; Neurons; Neurotransmitters; Optical Methods; Optics; Palate; Parents; Physiological; Positioning Attribute; Property; Pyramidal Cells; Relative (related person); Research; Resolution; Signal Transduction; Sum; Synapses; System; Techniques; Technology; Testing; Thiophenes; Time; Vertebral column; Work; choline analog; chromophore; design; fluorescence imaging; forging; functional group; gamma-Aminobutyric Acid; hippocampal pyramidal neuron; mimetics; neuronal cell body; neurophysiology; neurotransmission; new technology; photolysis; postsynaptic; presynaptic; programs; research study; response; signal processing; tool; two-photon

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.

描述（由申请人提供）：该提案的目标是开发和测试用于神经递质双光子释放的新光学技术。我们以前开发的笼状神经递质已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状化合物至关重要，因为它是定义探针的生物学问题。在这个建议中，我们试图解决一个重要的差距，用于光化学探测神经元功能的光化学方法，即能够完成同时，多模式的光学控制的并行信号处理。在上一个资助周期中，我们对发色团进行了新的笼化，该发色团可以在长波长的光下以几乎完全的颜色选择性被光解，同时在短波长下具有基本的光稳定性。我们建议将此探针测试问题有关的兴奋性和抑制性信号在锥体细胞的整合。我们还将继续开发化学探针，研究笼状化合物的脱靶药理作用，并开发具有扩展π电子系统的新笼状化合物。该提案的总体目标是开发新的光化学工具，允许树突状信号传导过程的双向光学控制。