CELLULAR/MOLECULAR ANALYSIS OF SHORT & LONG TERM MEMORY

本研究项目的长期目标是分析一个由巴甫洛夫条件反射产生的联想学习和记忆的细胞和突触机制。这项研究将提供对一次和多次条件反射后联想经验的一般记忆原理的见解，并有助于阐明记忆转化为更持久的形式——长期记忆所必需的事件。为了实现这些目标，将在海洋软体动物Hermissenda中开展一项多学科方法来研究联想学习和记忆，这一准备工作已被证明在生物物理和生物化学学习研究中有用。这项研究将结合细胞神经生理学、生物物理学、生物化学和行为技术来研究完整和孤立的神经系统的短期和长期记忆。该研究的一个主要目标是确定合成和/或磷酸化受一次试验和多次试验巴甫洛夫条件作用调节的蛋白质。我们将通过检查信号转导通路在单试验和多试验条件作用下不同记忆阶段的贡献来补充条件作用调节蛋白质的研究。我们最近发现了一种与记忆巩固中间阶段相关的-胸腺素样蛋白（CSP24）。CPS24在单试和多试条件作用下记忆巩固的时间依赖性过程中的具体作用有待进一步研究。Hermissenda的CS通路在条件动物的鉴定细胞中支持可塑性的两个例子；突触促进或增强和兴奋性增强。我们将确定是否相似或不同的潜在生化机制支持CS通路中已识别细胞的可塑性的两个例子，并检查细胞和突触机制与个体条件动物行为之间的关系。该项目的另一个目标是确定和比较巴甫洛夫条件反射消退的基本机制与条件反射保留（遗忘）的时间依赖性变化。总的来说，这些学习和记忆的研究将有助于阐明短期和长期记忆的基本机制，并为记忆机制与临床记忆障碍之间的关系提供见解。

The long-term objective of this research project is to analyze the cellular and synaptic mechanisms of an example of associative learning and memory produced by Pavlovian conditioning. The studies proposed in this grant renewal will provide insights into general principles underlying memory for an associative experience following one-trial and multi-trial conditioning, and contribute to the elucidation of the events that are essential for the transformation of memory into a more enduring form, long- term memory. To address these goals, a multi-disciplinary 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 biochemical 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 to identify proteins whose synthesis and/or phosphorylation are regulated by one-trial and multi-trial Pavlovian conditioning. We will compliment our studies of proteins regulated by conditioning by examining the contributions of signal transduction pathways to different stages of memory following one-trial and multi-trial conditioning. We have recently identified a beta-thymosin-like protein (CSP24) that is associated with an intermediate stage of memory consolidation. Studies are proposed to determine the specific role of CPS24 in time-dependent processes of memory consolidation produced by one- trial and multi-trial conditioning. The CS pathway of Hermissenda supports two examples of plasticity in identified cells of conditioned animals; synaptic facilitation or enhancement and enhanced excitability. We will determine if similar or different underlying biochemical mechanisms support the two examples of plasticity in identified cells of the CS pathway and examine the relationship between the cellular and synaptic mechanisms and the behavior of individual conditioned animals. An additional goal of this project is to determine and compare basic mechanisms of extinction of Pavlovian conditioning with time-dependent changes in retention of conditioning (foretting). Collectively, these studies of learning and memory will help to elucidate basic mechanisms of short- and long-term memory and provide insights into the relationship between memory mechanisms and clinical disorders of memory.