CELLULAR-BEHAVIORAL ANALYSIS OF SHORT & LONG-TERM MEMORY

这是一项在ADAMHA研究下提供五年支持的请求 科学家发展奖计划。长期目标是 研究项目是分析细胞和分子机制， 联想学习和记忆的例子。本报告中提出的研究 格兰特将提供深入了解记忆的一般原则， 一个关联的经验后，一次试验条件反射，并有助于 对记忆转变至关重要的事件的阐释 转化为更持久的形式长期记忆为了实现这些目标，A 联想学习和记忆的多学科研究方法 将在海洋软体动物Hermissenda中进行， 已被证明在学习的生物物理和分子研究中是有用的。的 研究将使用细胞神经生理学， 生物物理，生物化学和行为技术，以研究短期和 在完整和孤立的神经系统中的长期记忆。一个主要目标 这项研究的一部分是对蛋白质的贡献的调查， 磷酸化对诱导的时间依赖性过程， 短期和长期记忆的维持和表达。 近期 发现用广谱激酶抑制蛋白激酶C 抑制剂或通过下调来消耗激酶水平， 诱导短期记忆，而不是长期记忆， 不同的分子机制可能是这两个阶段的基础 记忆。建议进一步研究解离 短期和长期记忆之间的联系， 激酶和蛋白质磷酸化可能导致诱导， 维持和表达不同的记忆阶段。第二个目标是 这个项目是分析特定的膜电导， 通过一次试验条件反射进行修改，并确定 增强的兴奋性和突触强度的修改， 长期记忆的表达。第三个主要目标是确定 运动背后的神经回路并形成半完整的 运动神经元同时记录和测量的制剂 行为的条件性改变。这些研究有助于 阐明短期和长期记忆的基本机制，以及这些机制如何 机制可能与临床记忆障碍有关。

This is a request for five years of support under the ADAMHA Research Scientist Development Award Program. The long-term objective of this research project is to analyze the cellular and molecular mechanisms of an example of associative learning and memory. The studies proposed in this grant will provide insights into general principles underlying memory for an associative experience following one-trial conditioning, and contribute to the elucidation of the events critical for the transformation of memory into a more enduring form, long-term memory. Toward these goals, a multidisciplinary approach to the study of associative learning and memory will be carried out in the marine mollusc Hermissenda, a preparation that has proven useful in biophysical and molecular studies of learning. The research will use a combination of cellular neurophysiological, biophysical, biochemical, and behavioral techniques to study short and long-term memory in intact and isolated nervous systems. One primary goal of the research is an investigation of the contribution of protein phosphorylation to the time-dependent processes underlying the induction, maintenance and expression of short- and long-term memory. The recent discovery that inhibiting protein kinase C with broad spectrum kinase inhibitors or depleting kinase levels by down-regulation, blocks the induction of short-term, but not long-term memory provides additional evidence that different molecular mechanisms may underlie these two phases of memory. Studies are proposed to further investigate the dissociation between short and long-term memory and the contribution that protein kinases and protein phosphorylation may make to the induction, maintenance, and expression of different memory stages. A second goal of this project is to analyze the specific membrane conductances that are modified by one-trial conditioning, and identify the contribution of enhanced excitability and modifications in synaptic strength to the expression of long-term memory. The third major goal is to identify the neural circuitry underlying locomotion and develop a semi-intact preparation for simultaneously recording from motor neurons and measuring conditioned modification of behavior. These studies should help to elucidate basic mechanisms of short and long-term memory and how such mechanisms may be related to clinical disorders of memory.