Neurochem Chip: Study of Neurotransmitter Release

描述：（申请人提供） 记录神经递质释放的能力完全不受限制 研究药物滥用对产前动物的影响， 药物滥用和转基因小鼠的青少年模型，一直是有限的，甚至 高不可攀我们建议开发一种叫做神经化学芯片的技术。这 这项技术涉及到微型传感器的开发， 专门测量神经化学物质，如谷氨酸和GABA，使用 电子照相设计的微电极和自参考记录 approach.在第一阶段的提案中，神经化学芯片将被集成到 聚酰亚胺柔性电缆， 记录额叶皮层神经递质的释放， 纹状体和海马区。试点研究和 先前的工作支持Neurochem Chip可以使用 自我参照记录范式然而，技术的改进是 为了在清醒的行为动物中进行这种记录， 为研制完全不系留的记录系统奠定了基础 涉及遥测技术。此外，一个新的原型传感器，将 允许同时测量谷氨酸和GABA， 研究了在第二阶段，记录电路将小型化， 将开发一个总的遥测系统，以便大量的老鼠和 老鼠可以记录。总的来说，这些技术将允许快速 筛查滥用药物对大脑神经递质系统的影响， 急性和慢性，在成年和发育中的大鼠和小鼠， 无法使用现有技术进行。此外，神经化学芯片可以 可能被开发来测量大量的其他神经递质。

DESCRIPTION: (provided by the applicant) The capability to record neurotransmitter release in totally unrestrained animals to study the effects of drugs of abuse in prenatal animals, rat adolescent models of drug abuse and transgenic mice, has been limited, or even unattainable. We propose to develop a technology we call Neurochem Chip. This technology involves the development of microsensors that are capable of nearly specifically measuring neurochemicals such as glutamate and GABA, using photolithographically designed microelectrodes and a self-referencing recording approach. In this Stage 1 proposal, Neurochem Chips will be integrated to polyimide flex cables in order to carry out recordings of neurotransmitter release in the frontal cortex, striatum and hippocampus in tethered, awake behaving rats. Pilot studies and prior work support that Neurochem Chip can reliably measure L-glutamate using a self-referencing recording paradigm. However, refinements in technology are needed in order to carry out such recordings in the awake behaving animal to lay the foundation for the development of a totally untethered recording system involving telemetry technology. In addition, a new prototype sensor that will allow for the simultaneous measures of both glutamate and GABA will be investigated. In Stage 2, the recording circuitry will be miniaturized and a total telemetric system will be developed so that large numbers of rats and mice can be recorded. In general, these technologies will allow for the rapid screening of the effects of drugs of abuse on brain neurotransmitter systems, acutely and chronically, in both adult and developing rats and mice which cannot be carried out using current technology. In addition, Neurochem Chip can possibly be developed to measure a large number of other neurotransmitters.