NEURAL BASIS OF COMPLEX BEHAVIORS

我之所以申请这个奖项，是因为我正处于职业生涯的关键阶段。五年前，我获得了终身教职的任命，并成立了一个独立的实验室。我的目标是进入一个研究领域，它建立在我以前训练的基础上，但极大地扩展了我的调查领域。作为一名博士后，我描述了海兔摄食神经肌肉系统可塑性的重要细胞机制。在我自己的实验室里，我不希望被局限于神经肌肉系统。显然，许多形式的行为可塑性都是由中枢神经系统调节的。我认为研究摄食回路的可塑性将是有利的，因为摄食神经肌肉系统的特征是如此之好。因此，行为可塑性可以用一种综合的方式来研究，也就是说，既可以外围研究，也可以中心研究。为了承担这项工作，我必须提高我的技术熟练程度(例如，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投入到研究中。作为这种密集努力的结果，我发表了几篇非神经肌肉学论文。然而，在1999年，我的K02奖将到期，我将承担重大的教学和行政责任，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，我已经确定了感觉神经元会在正在进行的行为中触发立即表现出来的变化，以及在感觉神经元不再活跃后表现出来的变化(即，就像感觉活动的“记忆”)。我提出了一些假设，假设有趣而新颖的细胞机制调节感觉诱导的运动输出变化。在拟议的研究中，我想获得检验这些假设所需的专业知识。例如，我会使用声波显微测量学来测量实际的进食运动，使用计算技术来解决生物物理问题，以及使用分子生物学技术来表征感觉神经元中存在的调制共递质。我还提出了一些实验，这些实验将开始一条新的调查路线，因为我将描述一种新的进食行为开始的情况。我会将新行为的启动与之前描述的正在进行的行为的修改进行对比。这些实验可能会提供对神经系统功能障碍的见解，当正确选择行为所需的认知过程受到干扰时，就会发生这种情况，就像强迫症和强迫症一样。因此，这项研究与NIMH的任务直接相关。

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in an ongoing behavior that are manifested immediately, and changes that are manifested after sensory neurons are no longer active (i.e., like a "memory" of sensory activity).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.