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: 9043241
• 负责人: Nigel T Maidment
• 金额: $ 6.44万
• 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/9043241
• 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）：通过同时且近实时地测量大脑中的多个神经活性分子的方法，将极大地促进理解网络内的神经元如何相互作用以控制行为的努力。 现有方法要么提供单一分析物的快速测量（例如，快速扫描循环伏安法），要么提供时间分辨率不足的多种分析物测量（微透析）。 在这里，我们将开发一种植入式微探针，能够同时快速监测 3 种普遍存在的神经递质/神经调节剂：多巴胺 (DA)、谷氨酸 (Glut) 和乙酰胆碱 (ACh)。 此外，我们将通过将光波导合并到微探针中来利用光遗传学的力量，为与微电极阵列上的每个传感电极并置的组织提供定向照明。 这将通过采用创新的二氧化硅基微探针设计来实现，该微探针设计具有嵌入式波导和分光器，并在每个微电极下方嵌入微镜以实现均匀的定向光照明。 由此产生的微探针将结合基因分离的神经元末端的局部调制与这些末端的递质释放的测量，以及网络内神经元释放的其他递质的最终变化，所有这些都在自由行为动物的背景下进行。 由于 DA、Glut 和 ACh 作为多个大脑区域中的神经元间信号分子，控制从学习、记忆到运动控制等多种功能，这些传感器将在广泛的神经科学应用中带来变革。 我们对其体内表现的评估将集中在纹状体，这是一个涉及运动控制和动机行为的大脑区域。 多个递质释放事件与行为动作的精确耦合将为寻找多种神经和精神疾病的治疗干预措施提供有价值的信息。