Collaborative Research: The neurobiology of dopamine in the leech and the modulation of locomotor behaviors

该奖项是根据2009年《美国复苏和再投资法案》(Public Law 111-5)资助的。多巴胺(DA)是一种重要的、通用的运动控制调节器，但神经科学家尚未确切地确定含有DA的神经元及其靶向电路如何编排特定的运动程序。在研究高等脊椎动物系统中运动的控制和启动方面，这是一项特别艰巨的任务。与运动调节有关的问题是决策的想法，以及如何选择一种运动形式而不是另一种形式，例如，在爬行和游泳之间进行选择。这一合作研究项目正在单个识别的神经元水平上解决这些重要问题；通常在完好无损的动物行为时。被选为研究对象的是水蛭较为简单的神经系统，因为它包含相对较大的、在生理上可以接触到的神经元和分层的电路组织，从而促进了对运动、身体运动和下行控制的研究。具体地说，合作研究团队正在表征爬行相关行为背后的模式生成网络的组成部分，并确定DA如何改变神经元的属性以促进它们参与爬行。这种方法将自然而然地导致对决策的神经元基础的理解，因为已经发现，每当DA触发爬行时，游泳就被抑制。合作研究团队将使用各种行为学、电生理学和解剖学方法来研究DA如何促进爬行行为。他们还将使用最先进的电压敏感染料成像系统对受DA影响的神经元电路进行成像。许多正在进行的实验涉及研究生和本科生。其他实验，稍作修改，纳入了更年轻的K-12学生的参与。圣奥拉夫学院是一家仅面向本科生的研究机构，与克里斯普博士的合作提供了额外的、有价值的本科生培训和指导机会交流。该提案的项目和技术组成部分具有内在的综合性，涵盖从动物行为到细胞生物学/神经生物学、计算神经科学、物理学和工程学等多个学科。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).Dopamine (DA) is an important and universal modulator of motor control, but neuroscientists have yet to determine precisely how DA-containing neurons and their targeted circuitry choreograph specific locomotor programs. This has been an especially daunting task in studying the control and initiation of locomotion in higher vertebrate systems. Related to this issue of locomotor regulation is the idea of decision-making, and how one form of locomotion is selected instead of another, for example, the choice between crawling vs. swimming. This collaborative research project is addressing such important questions at the level of single identified neurons; often at times while the intact animal is behaving. The simpler nervous system of the leech, Hirudo medicinalis, was selected for study because it contains relatively large and physiologically accessible neurons and a hierarchical circuit organization, thus facilitating studies of locomotion, body movement and descending control. Specifically, the collaborative research team is characterizing constituents of the pattern-generating network underlying crawling-related behavior, and determining how DA changes the properties of neurons to facilitate their participation in crawling. This approach will lead naturally to an understanding of the neuronal bases of decision-making, because it has been found that whenever DA triggers crawling then swimming is inhibited. The collaborative research team will use a variety of behavioral, electrophysiological, and anatomical methods to study how DA promotes crawling behavior. They will also image neuronal circuits influenced by DA using a state-of-the-art voltage sensitive dye imaging system. Many of the experiments being conducted involve graduate and undergraduate students. Other experiments, with minor modification, incorporate the participation of younger K-12 students. The collaboration with Dr. Crisp at St. Olaf College, an undergraduate-only research institution, provides an additional and valuable exchange of undergraduate training and mentoring opportunities. The projects and technological components of the proposal are inherently integrative, spanning disciplines from Animal Behavior to Cell Biology/Neurobiology, Computational Neuroscience, Physics, and Engineering.