Fiber-Optic Devices for Uncaging of Neurotransmitters

描述(由申请人提供)： 该提案的目标是开始开发和测试一种工具，该工具可以以与生理记录技术范围兼容的方式提供对深层神经组织的焦点控制，包括兴奋、抑制和调制状态。我们正在设计和测试的工具是一种光纤光导系统，用于对笼子中的神经递质进行聚焦灌封。该系统将与神经记录和神经递质测量技术相结合。这样的组合系统将允许通过突触后机制对靶组织进行快速兴奋、抑制和/或调制，同时不会为记录组件引入电子噪声。还有可能对活动和递质水平进行反馈调节。为了测试该工具，因为它是迭代原型，我们将使用几个动物模型，这些模型在我们的实验室中得到了很好的建立和理解。 本项目有三个具体目标：1.具体目标1.构建和优化植入式光纤注入系统和记录装置，作为实验工具，用于脑深部刺激和其他神经假体。具体目的2开发笼式甘氨酸、5-羟色胺和多巴胺，用于光纤系统的实验和未来临床应用。具体目的3在哺乳动物中枢神经系统中，首先在急性准备(猫脊髓)中，然后在慢性准备(大鼠臂旁核)中，使用生理和行为分析来验证所开发的装置和笼养材料。

DESCRIPTION (provided by applicant): The goal of the proposal is to begin to develop and test a tool that can provide focal control of deep neural tissues including excitation, inhibition and modulation state in a fashion compatible with the range of physiological recording techniques. The tool we are designing and testing is a fiber optic light guide system, which is used for focal uncaging of caged neurotransmitters. This system will be coupled with neural recording and neurotransmitter measurement techniques. Such a combined system will allow rapid excitation, inhibition and/or modulation of target tissues, via post-synaptic mechanisms, while introducing no electrical noise for the recording components. There will also be the potential for feedback regulation of activity and of transmitter levels. To test the tool as it is iteratively prototyped we will use several animal models that are well established and understood in our laboratories. Our project has three Specific Aims: 1. Specific Aim 1 Construction and optimization of an implantable fiber optic uncaging system and recording device for use as an experimental tool, in deep brain stimulation and in other neuroprostheses. Specific Aim 2 Development of caged glycine, serotonin and dopamine for experimental and future clinical applications with the fiberoptic system. Specific Aim 3 Validation of developed devices and caged materials in mammalian CNS using physiological and behavioral assays, first in an acute preparation (cat spinal cord), and then in a chronic preparation (rat parabrachial nucleus).