Multifunctional Microprobe for Multiple Neurotransmitter Sensing and Optogenetics

用于多种神经递质传感和光遗传学的多功能微探针

• 批准号: 9037075
• 负责人: Nigel T Maidment
• 金额: $ 51.6万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9037075
• 关键词: Acetylcholine; Acute; Animals; Area; Behavior; Behavior Control; Behavior monitoring; Behavioral; Biosensor; Boron; Brain; Brain region; Carbon Dioxide; Chemicals; Chronic; Complex; Corpus striatum structure; Coupling; Deposition; Detection; Development; Devices; Diamond; Dopamine; Effectiveness; Electrodes; Electroplating; Engineering; Evaluation; Event; Film; Glutamates; Goals; Health; Hydrogen Peroxide; Individual; Investigation; Lasers; Learning; Light; Lighting; Longevity; Measurement; Measures; Memory; Mental disorders; Methods; Microdialysis; Microelectrodes; Microinjections; Monitor; Nature; Nerve; Neurologic; Neuromodulator; Neurons; Neurosciences; Neurotransmitters; Noise; Optics; Output; Oxidases; Performance; Phase; Population; Printing; Production; Publishing; Rattus; Rodent; Scanning; Shapes; Signaling Molecule; Silicon Dioxide; Site; Source; Techniques; Technology; Testing; Therapeutic Intervention; Time; Tissues; Validation; Work; base; biomaterial compatibility; brain tissue; design; enzyme immobilization; extracellular; implantable device; implantation; in vivo; innovation; microsensor; motivated behavior; motor control; nervous system disorder; neural circuit; neurochemistry; neurotransmission; neurotransmitter release; optogenetics; relating to nervous system; research study; sensor; temporal measurement

DESCRIPTION (provided by applicant): Efforts to understand how neurons within networks interact to control behavior will be greatly facilitated by a means with which to measure multiple neuroactive molecules in the brain simultaneously and in near-real time. Existing methods either offer rapid measurements of a single analyte (e.g., fast-scan cyclic voltammetry) or provide multiple analyte measurement with insufficient temporal resolution (microdialysis). Here, we will develop an implantable microprobe capable of simultaneous rapid monitoring of 3 ubiquitous neurotransmitters/neuromodulators: dopamine (DA), glutamate (Glut), and acetylcholine (ACh). Further, we will harness the power of optogenetics by incorporating an optical waveguide into the microprobe providing directional illumination of tissue juxtaposed to each sensing electrode on the microelectrode array. This will be achieved using an innovative silica-based microprobe design with embedded waveguides and light splitters, and with a micromirror embedded underneath each microelectrode for uniform directional light illumination. The resultant microprobe will combine local modulation of genetically isolated neuron terminals with measurement of transmitter release from those terminals, together with resultant changes in the release of other transmitters from neurons within the network, all in the context of a freel behaving animal. These sensors will be transformative in a wide range of neuroscience applications due to the involvement of DA, Glut and ACh as inter-neuronal signaling molecules in multiple brain regions controlling a plethora of functions from learning and memory to motor control. Our evaluation of their performance in vivo will focus on the striatum, a brain region involved in motor control and motivated behavior. Precise coupling of multiple transmitter release events to behavioral actions will provide valuable information pertinent to the search for therapeutic interventions for multiple neurological and psychiatric disorders.

描述（由申请人提供）：了解网络中的神经元如何与控制行为相互作用的努力将通过一种在同时且近乎真实的时间同时测量大脑中的多个神经活性分子的方法来大大促进。 现有方法可以快速测量单个分析物（例如快速扫描的循环伏安法），或提供多个分析物测量，而时间分辨率不足（微透析）。 在这里，我们将开发一种可植入的微型探针，能够同时快速监测3个无处不在的神经递质/神经调节剂：多巴胺（DA），谷氨酸（GLUT）和乙酰胆碱（ACH）。 此外，我们将通过将光学波导掺入微探针中，从而利用光遗传学的功能，从而提供与微电极阵列上每个感应电极并列的组织的定向照明。 这将是使用具有嵌入式波导和光拆分器的创新的基于二氧化硅的微型探针设计来实现的，并在每个微电极下方都嵌入微骨，以均匀地定向光照明。 所得的微探针将结合遗传学分离的神经元末端的局部调节，并结合从这些末端释放发射机释放的局部调节，以及在网络中其他神经元的释放的变化，这都是在自由行为的动物的背景下。 由于DA，GLUT和ACH作为神经元信号分子的参与，这些传感器将在多个神经科学应用中具有变化，这些传感器在多个大脑区域中涉及到神经元信号分子，这些区域控制着从学习和记忆到运动控制的众多功能。 我们对他们在体内表现的评估将集中在纹状体上，纹状体是参与运动控制和动机行为的大脑区域。 多个发射器释放事件与行为动作的精确耦合将提供与寻求多种神经和精神疾病的治疗干预措施有关的有价值的信息。