Functional Analysis of the Mesolimbic Dopamine System

描述（由申请人提供）：从腹侧被盖区（VTA）到伏隔核（NAc）的中边缘多巴胺投射与许多药物滥用的神经生物学作用有关。然而，该系统的复杂性对其功能的研究构成了重大障碍。因此，科学家们研究了它的碎片成分。在这项工作中，快速扫描循环伏安法将用于测量NAc中多巴胺浓度的亚秒变化，同时在NAc和VTA中进行双通道细胞外电生理记录神经元活动。电化学数据将采用主成分回归分析，使多巴胺浓度的变化与其他电化学因素客观区分，并有选择地定量。这种结合的方法将允许确定快速释放多巴胺和这条通路两端的电活动之间的精确关系。NAc中探针的大小将被优化，以提供被采样的突触集成的几何信息。一旦确定了特征，该方法将被用于研究可卡因对这种与奖励相关的大脑回路的影响。

DESCRIPTION (provided by applicant): The mesolimbic dopamine projection from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) has been implicated in the neurobiological actions of many drugs of abuse. However, the complexity of this system presents a significant barrier to investigation of its function. Thus, scientists have studied its components in fragments. In the proposed work, fast-scan cyclic voltammetry will be used to measure subsecond changes in dopamine concentration in the NAc with dual channel extracellular electrophysiology recordings of neuronal activity taken simultaneously in both the NAc and VTA. The electrochemical data will be analyzed with principal component regression, allowing dopamine concentration changes to be objectively distinguished from other electrochemical contributors and selectively quantitated. This combined approach will allow for the determination of the precise relationship between rapid dopamine release and the electrical activity at both ends of this pathway. The size of the probe in the NAc will be optimized to provide information on the geometry of the synaptic ensembles being sampled. Once characterized, the methodology will be used to investigate the effects of cocaine on this reward-related brain circuitry.