NEURAL BASIS OF COMPLEX BEHAVIORS

我申请这个奖项是因为我正处于职业生涯的关键阶段。五年前，我被任命为终身教授，并成立了一个独立的实验室。我的目标是进入一个建立在我以前的训练基础上的研究领域，但这大大扩展了我的研究领域。作为一名博士后，我在澳大利亚研究了对喂养神经肌肉系统可塑性重要的细胞机制。在我自己的实验室里，我不希望局限于神经肌肉系统。很明显，许多形式的行为可塑性是由中枢神经系统介导的。我觉得研究进食回路的可塑性是有好处的，因为进食神经肌肉系统已经有了很好的特征。因此，行为可塑性可以以综合的方式进行研究，即从外围和中心两方面进行研究。为了承担这项工作，我必须提高我的技术水平（如熟悉电压钳），我必须加强我的理论技能。因此，我申请了K02奖，这样我就可以把大部分时间用于研究。由于这种密集的努力，我发表了几篇与神经肌肉无关的论文。然而，在1999年，我的K02奖将到期，我将承担重要的教学和行政责任，并减少我投入研究的时间。因此，我将无法完成我已经开始的工作。也就是说，我已经确定了在正在进行的行为中触发立即表现的变化的感觉神经元，以及在感觉神经元不再活跃（即，像感觉活动的“记忆”）之后表现出来的变化。我提出了一些假设，假设有趣而新颖的细胞机制介导了运动输出中感觉诱导的变化。在拟议的研究中，我希望获得检验这些假设所需的专业知识。例如，我会用声学测量法来测量实际的进食运动，用计算技术来解决生物物理问题，用分子生物学技术来表征存在于感觉神经元中的调节共递质。我还提出了一些实验，这些实验将开始一条新的研究路线，我将描述一种新的摄食行为被启动的情况。我将把一个新行为的开始与一个正在进行的行为的先前有特征的修改进行对比。这些实验可能会让我们深入了解神经系统的功能障碍，当正确选择行为所必需的认知过程受到干扰时，就会发生这种功能障碍，就像强迫症和强迫症一样。因此，这项研究与NIMH的使命直接相关。

I am requesting this award because I am at a critical stage in my career. Five years ago I obtained an appointment as a tenure-track faculty member and set up an independent laboratory. My goal was to move into a line of research that build upon my previous training but which significantly expanded my field of inquiry. As a postdoc I characterized cellular mechanisms important for plasticity in a feeding neuromuscular system in Aplysia. In my own laboratory I did not wish to be restricted to neuromuscular systems. Obviously, many forms of behavioral plasticity are mediated in the central nervous system. I felt that it would be advantageous to study plasticity in the feeding circuitry since feeding neuromuscular systems are so well characterized. Behavioral plasticity can, therefore, be studied in an integrated way, i.e., both peripherally and centrally. To undertake this work I had to increase my technical proficiency (e.g., become familiar with voltage clamp) , and I had to strengthen my theoretical skills. Consequently, I applied for a K02 award so that I could devote the majority of my time to research. As a result of this intensive effort I published several non-neuromuscular papers. In 1999, however, my K02 Award will expire and I will be expected to assume significant teaching and administrative responsibilities, and reduce the time I devote to research. I will, therefore, not be able to complete what I have started. Namely, I have identified sensory neurons that trigger changes in an ongoing behavior that are manifested immediately, and changes that are manifested after sensory neurons are no longer active (i.e., like a "memory" of sensory activity). I have generated hypotheses that postulate that interesting and novel cellular mechanisms mediate sensory-induced changes in motor output. In proposed research I would like to acquire the expertise I need to test these hypotheses. For example, I would use sonomicrometry to measure actual feeding movements, computational techniques to address biophysical issues, and molecular biological techniques to characterize modulatory co-transmitters present in sensory neurons. I also propose experiments that will begin a new line of investigation in that I will characterize a situation where a new feeding behavior is initiated. I will contrast the initiation of a new behavior with the previously characterized modification of an ongoing behavior. These experiments may provide insights into dysfunctions of the nervous system that occur when cognitive processes necessary for the proper choice of behavior are perturbed, as is the case with obsessions and compulsions. Thus, this research is directly relevant to the mission of the NIMH.