Mechanisms of Appetitive and Aversive Context Learning

描述(由申请人提供)：背景变量在许多精神障碍的发展、治疗和复发中发挥重要作用，包括创伤后应激障碍、抑郁和药物滥用。了解允许获得背景信息的机制对于开发这些疾病的治疗方法至关重要。对情境学习的研究也有助于确定作为学习和记忆基础的联想和神经生物学机制。在神经生物学层面，关于情境学习的大部分已知知识来自对情境诱发恐惧的分析，这是一种强大的依赖于海马体的学习过程，发生在条件情境中的一次电击之后。对近交系和转基因小鼠背景恐惧的研究有助于描绘记忆的许多遗传和分子机制。这个B/Start应用程序中的两个特定目标旨在扩大对小鼠情境学习的分析，以包括情境恐惧条件反射和食欲情境条件反射。在特定目标1，C57BL/6和DBA小鼠，这两个近交系小鼠在情境恐惧方面有很好的记录差异，将使用杂志方法比较情境恐惧和食欲情境条件反射的获得和表达。通过使用几种不同的条件反射方案，我将能够确定语境学习缺陷从厌恶准备到渴望准备的程度。在具体目标2中，我们将考察食欲语境条件反射的联想结构，以确定语境条件反射过程中形成的联想的内容。这一目标的实验将使我能够评估背景-反应和背景-结果关联对行为的相对贡献。这些实验将为一个研究项目奠定基础，该项目专注于对学习和记忆中特定背景联系的性质提出问题。

DESCRIPTION (provided by applicant): Contextual variables play important roles in the development, treatment, and relapse of many psychiatric disorders, including posttraumatic stress disorder, depression, and substance abuse. Understanding the mechanisms that allow contextual information to be acquired has been critical to the development of treatments for these disorders. The study of contextual learning has also been instrumental in determining the associative and neurobiological mechanisms that underlie learning and memory in general. At the neurobiological level, much of what is known about contextual learning comes from the analysis of context evoked fear, a robust hippocampus-dependent learning process that occurs after a single experience of a shock in a conditioning context. Studies of contextual fear in inbred and genetically modified mice have helped to delineate many of the genetic and molecular mechanisms of memory. The two specific aims in this B/START application are designed to expand the analysis of contextual learning in mice to include both contextual fear conditioning and appetitive contextual conditioning. In Specific Aim 1, C57BL/6 and DBA mice, two inbred strains with well-documented differences in contextual fear, will be compared in acquisition and expression of contextual fear and appetitive contextual conditioning using a magazine approach procedure. By using several different conditioning protocols, I will be able to determine the extent to which contextual learning deficits generalize from aversive to appetitive preparations. In Specific Aim 2, the associative structure of appetitive contextual conditioning will be examined to determine the content of the association that is formed during contextual conditioning. Experiments in this aim will allow me to assess the relative contribution of context-response and context-outcome associations to behavior. These experiments will lay the groundwork for a research program that is focused on asking questions about the nature of specific contextual associations in learning and memory.