Neurochem Chip: Methodology to Study Untethered Rats

描述（由申请人提供）：此II期CEBRA申请涉及开发神经化学芯片微电极，用于大鼠和小鼠神经递质释放的神经化学记录。该项目的长期目标是开发神经化学芯片，用于快速体内记录自由运动大鼠和小鼠中枢神经系统中的谷氨酸、GABA、乙酰胆碱和胆碱。在技术开发中，我们将首先在大鼠和小鼠身上实施和改进神经化学芯片技术。首先，我们计划优化麻醉大鼠和小鼠的记录方法。这将涉及与薄膜技术公司、混合电路公司和克利夫兰医疗设备公司合作开发微电极。仪器开发将与PCB组装公司合作进行。我们将在体外和体内广泛记录麻醉大鼠前额皮质、纹状体和海马中谷氨酸、GABA、胆碱和乙酰胆碱的释放和摄取。有许多微电极、仪器和记录细节必须首先优化，以开发可靠的神经化学芯片。这些微电极记录将与谷氨酸和胆碱的微透析测量进行比较，以尝试和进一步验证该技术。随着这项资助的进展，改进和适应的技术将应用于清醒行为的大鼠和小鼠的研究。将开发用于清醒大鼠的4通道测量和小鼠的2通道记录的自由移动系绳系统。此外，将开发一种生物遥测系统，用完全不受束缚的系统记录老鼠的情况。这将有助于1)增加录音的信噪比，2)增加老鼠的活动自由，以及3)监测大量老鼠的潜力。这些研究的主要目标是开发可靠、敏感和选择性的神经化学芯片，用于快速（逐秒）测定大脑细胞外空间的神经化学物质。这项技术可能对涉及药物滥用、疾病模型和行为的神经递质系统的基础科学研究产生重大影响。由于在将这些技术传播给其他研究人员之前必须解决许多技术问题，因此需要这种CEBRA第二阶段机制。

DESCRIPTION (provided by applicant): This Stage II CEBRA application involves the development of Neurochem Chip microelectrodes for neurochemical recordings of neurotransmitter release in rats and mice. The long-term goals of this project are to develop Neurochem Chips for rapid in vivo recordings of glutamate, GABA, acetylcholine and choline in the CNS of freely moving rats and mice. In developing the technologies, we will first implement and improve the technologies of Neurochem Chips in rats and mice. First, we plan to optimize the recording approaches in the anesthetized rat and mouse. This will involve microelectrode development in corporation with Thin Film Technologies, Hybrid Circuits, Inc., and Cleveland Medical Devices, Inc. Instrumentation development will occur in cooperation with PCB Assembly, Inc. We will carry out extensive in vitro and in vivo recordings of glutamate, GABA, choline and acetylcholine release and uptake in the prefrontal cortex, striatum and hippocampus of anesthetized rats. There are numerous microelectrode, instrumentation, and recording details that must first be optimized to develop reliable Neurochem Chips. These microelectrodes recordings will be compared with microdialysis measures of glutamate and choline, to try and further validate the techniques. As this grant progresses, the refined and adapted technologies will be applied to studies in awake behaving rats and mice. Freely moving tethered systems will be developed for 4-channel measures in awake rats and 2-channel recordings in mice. In addition, a biotelemetric system will be developed to record from rats with a totally untethered system. This should contribute to 1) increased signal-to-noise of the recordings, 2) increased freedom of movement of the rats, and 3) the potential for monitoring large numbers of rats. The major goal of these studies is to develop Neurochem Chips that are reliable, sensitive and selective for the rapid (second-by-second) determination of neurochemicals in the extracellular space of the brain. This technology could have a major impact on basic science studies of neurotransmitter systems involving drug abuse, disease models and behavior. This CEBRA Stage II mechanism is needed, due to the number of technical issues that must be addressed before these techniques can be disseminated to other researchers.