NEURAL BASIS OF COMPLEX BEHAVIORS

复杂行为的神经基础

• 批准号: 6477007
• 负责人: ELIZABETH C CROPPER
• 金额: $ 9.71万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-12-01 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6477007
• 关键词: Aplysia; behavioral /social science research tag; electromyography; histology; neural information processing; neurochemistry; neuromuscular system; neuroregulation; nutrient intake activity; nutrition related tag; psychomotor function; sensorimotor system; sensory mechanism; swallowing; synapses

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in an ongoing behavior that are manifested immediately, and changes that are manifested after sensory neurons are no longer active (i.e., like a "memory" of sensory activity).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

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，并建立了一个独立的实验室。我的目标是进入一个以我之前的培训为基础的研究领域，但它显着扩展了我的探究领域。作为一名博士后，我描述了对海兔摄食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。显然，许多形式的行为可塑性都是由中枢神经系统介导的。我认为研究喂养回路的可塑性是有利的，因为喂养神经肌肉系统的特征非常明确。因此，行为可塑性可以以综合的方式（即外围和中心）进行研究。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），并且我必须加强我的理论技能。因此，我申请了 K02 奖项，这样我就可以将大部分时间投入到研究中。经过大量努力，我发表了几篇非神经肌肉论文。然而，到 1999 年，我的 K02 奖将到期，我将承担重要的教学和行政职责，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事情。也就是说，我已经确定了感觉神经元会触发立即表现出来的持续行为的变化，以及感觉神经元不再活跃后表现出的变化（即，就像感觉活动的“记忆”）。我提出了一些假设，假设有趣且新颖的细胞机制介导了感觉诱发的运动输出变化。在拟议的研究中，我想获得测试这些假设所需的专业知识。例如，我会使用声测法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，并使用分子生物学技术来表征感觉神经元中存在的调节共递质。我还提出了将开始新的研究路线的实验，因为我将描述启动新的进食行为的情况。我将把新行为的启动与先前对正在进行的行为进行特征化的修改进行对比。这些实验可以提供对神经系统功能障碍的见解，这种功能障碍是在正确选择行为所必需的认知过程受到干扰时发生的，就像强迫症和强迫症的情况一样。因此，这项研究与 NIMH 的使命直接相关。