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个光纤导光系统，它是用于集中解开笼状神经递质。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快速激发、抑制和/或调节靶组织，同时不为记录组件引入电噪声。还将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，这是很好地建立和理解我们的实验室。 我们的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撑开系统和记录装置，用作脑深部刺激和其他神经假体的实验工具。具体目标2开发笼状甘氨酸、5-羟色胺和多巴胺，用于光纤系统的实验和未来临床应用。具体目标3使用生理学和行为学试验在哺乳动物CNS中验证开发的器械和笼状材料，首先在急性制备（猫脊髓）中，然后在慢性制备（大鼠臂旁核）中。

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).