The Neurobiology of Dopamine in the Leech: Modulation of Locomotor and Feeding-Related Behaviors

获奖摘要：神经科学的一个重要目标是了解中枢神经系统如何做出决定，使动物能够表达一种行为而不是另一种行为。显然，决策过程需要多个运动程序相互协调。PI和Co-PI认为，这些重要的问题可以通过研究水蛭（Hirudo medicinalis）的模型神经系统来理解。水蛭更简单的神经系统为研究其行为的潜在机制提供了一个首要的系统。大的和生理上可接近的神经元的存在，加上一个层次组织，将促进运动和运动的细胞研究。此外，他们的研究将集中在神经调节化合物多巴胺（DA）的行为作用上，多巴胺是所有动物行为的重要调节剂。研究人员的目标是确定DA如何影响人们决定表达哪些行为。该研究的中心假设是水蛭神经系统中分泌DA的神经元网络在行为的选择和协调中起作用，这些行为是摄食的食欲阶段的一部分。提出了两个主要目的：1)测试DA是否改变了咬和搜索运动，2)确定当大脑中的命令样神经元在DA存在或不存在的情况下受到电刺激时，行为是如何改变的。作为这项研究的一部分，活体大脑神经元的活动将在行为动物身上进行测量，使用最先进的染料光学成像系统，其颜色和强度随着兴奋神经元的电压而变化。这些实验将揭示DA如何影响神经元群，使它们能够选择和塑造动物可以表达的一整套运动行为。由于DA在调节哺乳动物行为（如运动、动机和奖励）中起着重要作用，因此我们对DA、运动和喂养相关行为的研究可能具有广泛的科学意义。许多被提议的实验都是为大学生设计的，目的是让他们在职业生涯的早期参与到科学过程中来。

The Neurobiology of Dopamine in the Leech: Modulation of Locomotor and Feeding-Related BehaviorsKaren A. Mesce and William B. Kristan, Jr.AWARD ABSTRACTAn important aim of neuroscience is to understand how decisions are made in the central nervous system that enable an animal to express one behavior instead of another. Clearly, decision-making processes require that multiple motor programs are coordinated with each other. The PI and Co-PI contend that such important issues can be understood by studying the model nervous system of the leech (Hirudo medicinalis). The simpler nervous system of the leech offers a premier system in which to study the underlying mechanisms of behavior. The presence of large and physiologically accessible neurons, coupled with a hierarchical organization, will facilitate cellular studies of locomotion and movement. In addition, their studies will focus on the behavioral roles of the neuromodulatory compound dopamine (DA), an important regulator of behavior in all animals. The researchers aim to determine how DA influences decisions about which behaviors to express. The central hypothesis of the research is that the network of DA secreting neurons in the leech nervous system functions in the choice and orchestration of behaviors that are part of the appetitive phase of feeding. Two primary aims are proposed: 1) To test whether DA alters biting and searching movements, 2) To determine how behaviors switch when command-like neurons in the brain are electrically stimulated in the presence or absence of DA. As part of this study, the activity of living brain neurons will be measured in behaving animals using a state-of-the-art optical imaging system of dyes whose color and intensity changes with the voltage of excited neurons. Such experiments will reveal how DA can influence populations of neurons so that they can select and shape the suite of locomotory behaviors that an animal can express. Because DA plays such a major role in regulating mammalian behaviors (e.g., locomotion, motivation and reward), our studies of DA, locomotion and feeding-related behaviors will likely have broad scientific significance. Many of the proposed experiments have been designed to be performed by college students to involve them in the process of science early in their careers.