Neurochem Chip: Study of Neurotransmitter Release

描述：(申请人提供) 完全不受限制地记录神经递质释放的能力 动物研究药物滥用对胎儿期动物、大鼠的影响 青少年滥用药物的模型和转基因小鼠，已经受到限制，甚至 遥不可及。我们计划开发一种我们称之为神经化学芯片的技术。这 技术涉及到微型传感器的开发，这种传感器能够几乎 专门测量谷氨酸和GABA等神经化学物质，使用 光刻设计的微电极和自参考记录 接近。在这一阶段1提案中，NeuroChem芯片将集成到 聚酰亚胺软电缆，以便 进行额叶皮质神经递质释放的记录， 在被拴住的清醒行为的大鼠的纹状体和海马体。试点研究和 先前的工作支持神经化学芯片可以可靠地使用 自我引用记录范式。然而，技术上的改进是 需要在清醒的行为动物中进行这样的记录 为开发完全不受束缚的记录系统奠定基础 涉及遥测技术。此外，一种新的原型传感器将 允许同时测量谷氨酸和GABA将是 调查过了。在阶段2中，记录电路将被微型化，并且 发展全遥测系统，使大量的老鼠和 老鼠可以被记录下来。一般而言，这些技术将允许快速 药物滥用对脑神经递质系统影响的筛选， 急性和慢性地，在成年和发育中的大鼠和小鼠中 不能用目前的技术来实现。此外，神经化学芯片可以 可能会被开发出来用来测量大量其他神经递质。

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.