Fiber-Optic Devices for Uncaging of Neurotransmitters

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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).