CELLULAR/MOLECULAR ANALYSIS OF SHORT & LONG TERM MEMORY

本研究计划的长期目标是分析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。 在这次资助更新中提出的研究将提供对记忆的一般原则的见解，这些原则是在一次试验和多次试验条件反射后的联想经验，并有助于阐明记忆转化为更持久形式（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中进行多学科方法的联想学习和记忆研究，这是一种已被证明在生物物理和生物化学学习研究中有用的制剂。 这项研究将结合细胞神经生理学、生物物理学、生物化学和行为学技术，研究完整和孤立神经系统的短期和长期记忆。 这项研究的一个主要目标是确定蛋白质的合成和/或磷酸化受到一次试验和多次试验巴甫洛夫条件反射的调节。我们将补充我们的蛋白质调节调节的条件反射的研究，通过检查信号转导通路的贡献，不同阶段的记忆后，一次试验和多次试验条件反射。 我们最近发现了一种β-胸腺素样蛋白（CSP 24），它与记忆巩固的中间阶段有关。本研究旨在探讨CPS 24在单次和多次条件反射记忆巩固过程中的作用。 Hermissenda的CS通路支持条件动物的已鉴定细胞中的可塑性的两个实例;突触促进或增强和增强的兴奋性。 我们将确定是否相似或不同的潜在的生化机制支持的两个例子的可塑性，在确定的细胞的CS通路，并检查细胞和突触机制和行为之间的关系，个别条件动物。 这个项目的另一个目标是确定和比较巴甫洛夫条件反射与条件反射保留（foretting）随时间变化的基本机制。 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，并为记忆机制和记忆临床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.