Multiple Memory Phases of Aplysia

描述(由申请人提供)：我们对世界上发生的事件进行编码、存储信息并在以后检索信息的能力是生存所必需的。我们的记忆提供了将过去的事件整合为当前适应行为的基本能力。因此，从基础科学的角度来看，了解涉及记忆形成的大脑过程至关重要，因为它可以为认知行为的一个基本方面提供机械性的见解。这项研究的主要目标是通过使用一个强大的模型系统--海洋软体动物海兔--来阐明记忆的大脑机制，以建立在细胞和分子水平上表达的神经元可塑性与行为上表达的敏化持久记忆的特定阶段之间的直接联系。为了实现这一目标，有三个具体的目标：行为分析的目的是确定管理一系列时间离散记忆形式的敏感记忆形成的“规则”。特别重要的是，不同的训练模式在形成机械上截然不同的记忆形式方面所起的独特作用。突触分析将旨在建立行为分析中揭示的不同形式记忆的突触类似物，并确定在形成这些不同记忆中所起作用的突触机制。分子分析的目的是通过检查在记忆形成过程中参与改变突触强度的分子级联(基因、信息和蛋白质)来识别不同形式记忆的“分子图谱”。与公共健康相关：在记忆受损的情况下，尤其是在阿尔茨海默氏症、创伤后应激障碍以及意外或中风的受害者中，了解记忆背后的大脑机制的重要性可以得到特别的理解。因此，心理健康的一个主要挑战是基本了解参与正常记忆形成的大脑机制，以及当记忆因疾病或伤害而受损时，这些机制是如何受损的。这样的理解对于开发有效的治疗涉及记忆障碍的认知问题是必不可少的。

DESCRIPTION (provided by applicant): Our ability to encode the events that occur in our world, store that information, and then retrieve it at a later time is essential for survival. Our memory serves the essential capacity to integrate past events into current adaptive behavior. Thus, understanding brain processes involved in memory formation is of critical importance from a basic scientific perspective, as it can provide mechanistic insights into a fundamental aspect of cognitive behavior. The overarching goal of this research project is to elucidate brain mechanisms of memory by using a powerful model system, the marine mollusk Aplysia, to forge direct links between neuronal plasticity expressed at the cellular and molecular levels, and specific phases of enduring memory for sensitization expressed behaviorally. To accomplish this goal, there are three Specific Aims: A BEHAVIORAL ANALYSIS will be aimed at identifying the "rules" that govern memory formation for a range of temporally discrete forms of memory for sensitization. Of special importance will be the unique roles of different patterns of training in the formation of mechanistically distinct forms of memory. A SYNAPTIC ANALYSIS will be aimed at establishing synaptic analogs of the different forms of memory revealed in the Behavioral Analysis, and determining the synaptic mechanisms that are recruited into play in forming these diverse memories. A MOLECULAR ANALYSIS will be aimed at identifying "molecular profiles" for different forms of memory by examining the molecular cascades (the genes, messages and proteins) that are involved in altering synaptic strength during memory formation. Relevance to public health: The importance of understanding brain mechanisms underlying memory can be especially appreciated in cases where memory is impaired, such as in Alzheimer's Disease, Post-Traumatic Stress Disorders, and in victims of accidents or strokes. Thus a major challenge in mental health is to achieve a basic understanding of the brain mechanisms that are engaged in normal memory formation, and how those mechanisms are impaired when memory is compromised by disease or injury. Such an understanding is essential for developing effective therapies for cognitive problems involving memory impairment.