Mechanisms of compensation for loss of brain dopamine

描述（由申请人提供）：多巴胺（DA）是动物王国中重要的神经递质/神经调节剂。在人类中，DA系统的功能障碍会导致运动、认知和情感障碍。在遗传模型系统中可行的详细研究允许对负责特定行为的通路进行回路水平的定义，允许对DA合成进行详细的时间/空间控制，并有可能揭示与人类DA功能障碍疾病相关的新的神经机制。在这个提议中，我们研究了一种新的自发抑制多巴胺损失表型的子集。我们将使用遗传和分子技术来识别和表征导致这种抑制的遗传因素。我们的模型与早期帕金森病特别相关，其中一个描述不清的途径可以部分补偿DA水平的降低，延迟症状的出现。本建议的重点是这种补偿机制。

DESCRIPTION (provided by applicant): Dopamine (DA) is an important neurotransmitter/ neuromodulator throughout the animal kingdom. In humans, dysfunction of the DA system leads to motor, cognitive, and affective disorders. Detailed studies feasible in the genetic model system Drosophila melanogaster permit circuit level definition of pathways responsible for specific behaviors, allow for detailed temporal/spatial control of DA synthesis, and have the potential to uncover novel neural mechanisms relevant to human diseases of DA dysfunction. In this proposal, we study a novel and spontaneous suppression of a subset of dopamine-loss phenotypes. We will use genetic and molecular techniques to identify and characterize the genetic elements responsible for this suppression. Our model is particularly relevant to early stage Parkinson's disease, where a poorly described pathway can partially compensate for decreased DA levels, delaying appearance of symptoms. This proposal focuses on the mechanisms of this compensation.