Optical probes for controlling cellular function

用于控制细胞功能的光学探针

基本信息

批准号：
9302846
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
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-15 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9302846
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 Interneurons Lasers Light Location Methodology Methods MicroRNAs Microscopy Monitor Neurons Neurotransmitters Optical Methods Optics Palate Parents Pharmacology Physiological Positioning Attribute Process Property Pyramidal Cells Research Resolution Signal Transduction Sum Synapses System Techniques Technology Testing Thiophenes Time Vertebral column Work choline analog chromophore design experimental study fluorescence imaging functional group gamma-Aminobutyric Acid hippocampal pyramidal neuron mimetics multimodality neuronal cell body neurophysiology neurotransmission new technology photolysis postsynaptic presynaptic programs public health relevance response tool two-photon

项目摘要

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）：建议的目的是开发和测试神经递质的两光子未成范围的新光学技术。我们以前开发的笼中的神经递质已被全球许多研究小组广泛使用。我们工作的一个重要特征是，我们已经与著名的生理学家建立了长期合作关系。这些相互作用至关重要的是有用且重要的笼中化合物的发展，因为它是定义探针的生物学问题。在此提案中，我们试图解决光学化学方法领域的重要差距，该差距用于神经元功能的光化学探测，即，可以同时完成并行信号过程的多模式光学控制能力。在上一个赠款周期中，我们制作了新的笼子，可以在光的长波长下几乎完全的色度选择性，而在短波长下是必不可少的光稳定性。我们建议将此探测器应用于有关锥体细胞中兴奋性和抑制信号整合的问题。我们还将继续开发研究笼中化合物的靶标药理作用的化学探针，并使用扩展的PI电子系统开发新的笼子化合物。该提案的总体目标是开发新的光化学工具，以允许对树突状信号过程的双向光控制。