Mechanisms of synaptic dopamine signaling in the control of behavior

神经调节剂多巴胺对许多大脑功能都很重要：多巴胺神经元的丧失会导致 运动障碍，如帕金森氏症；多巴胺信号是滥用药物和 是奖赏和成瘾的神经生物学的组成部分；而多巴胺信号是治疗 治疗许多神经精神疾病。尽管它在大脑中很重要，但人们对它知之甚少 关于体内调节突触多巴胺释放的机制。尽管多巴胺对人体的影响 已经对单个细胞进行了广泛的研究，即多巴胺信号是如何被处理以改变动力学的 突触后神经元执行行为变化的机制还不是很清楚。显微镜下的蛔虫 线虫提供了使用强大的工具研究多巴胺信号的这些方面的机会 分子遗传学和体内电路分析。利用行为遗传学和新开发的方法 对行为动物神经回路的分析我们将(1)确定调节多巴胺的机制 对食欲刺激和突触后反应的释放，以及(2)确定转换的电路机制 多巴胺信号将事件转化为行为的持久变化。因为它古老而保守的功能 动物神经系统中的多巴胺信号，我们建议我们的研究也将取得进展 了解人脑多巴胺系统突触前和突触后的机制 发现认识和治疗与多巴胺能功能障碍相关的疾病的新方法 系统。

The neuromodulator dopamine is important for many brain functions: loss of dopamine neurons causes movement disorders, such as Parkinson’s disease; dopamine signaling is targeted by drugs of abuse and integral to the neurobiology of reward and addiction; and dopamine signaling is a therapeutic target for the treatment of many neuropsychiatric disorders. Despite its importance in the brain, relatively little is known about mechanisms that regulate synaptic dopamine release in vivo. And although the effects of dopamine on individual cells have been extensively studied, how dopamine signals are processed to change the dynamics of post synaptic neurons to execute changes of behavior is not well understood. The microscopic roundworm C. elegans offers the opportunity to study these aspects of dopamine signaling using powerful tools of molecular genetics and in vivo circuit analysis. Using behavioral genetics and newly developed methods for analysis of neural circuits in behaving animals we will (1) determine mechanisms that regulate dopamine release in response to appetitive stimuli and postsynaptic and (2) determine circuit mechanisms that transform dopamine signaling events into lasting changes in behavior. Because of the ancient and conserved functions of dopamine signaling in the animal nervous system, we propose that our studies will also advance understanding of pre- and postsynaptic mechanisms in dopamine systems of the human brain and accelerate discovery of new approaches to understanding and treating diseases linked to dysfunction of dopaminergic systems.