Mechanisms of Appetitive and Aversive Context Learning

描述（由申请人提供）：背景变量在许多精神疾病的发展、治疗和复发中起着重要作用，包括创伤后应激障碍、抑郁症和药物滥用。了解机制，使上下文信息被收购的发展至关重要的治疗这些疾病。对情境学习的研究也有助于确定一般学习和记忆的联想和神经生物学机制。在神经生物学水平上，我们对情境学习的了解大多来自对情境诱发恐惧的分析，这是一种依赖于校园的学习过程，发生在条件反射情境中的单一电击体验之后。对近亲繁殖和转基因小鼠的背景恐惧的研究有助于描述记忆的许多遗传和分子机制。本B/START应用程序中的两个具体目标旨在扩展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，C57 BL/6和DBA小鼠，两个近交系的背景恐惧的差异有充分的记录，将比较收购和表达的背景恐惧和食欲的背景条件，使用杂志的方法程序。通过使用几种不同的条件反射方案，我将能够确定情境学习缺陷从厌恶性准备推广到食欲准备的程度。在具体目标2中，我们将考察食欲语境条件作用的联想结构，以确定在语境条件作用过程中形成的联想的内容。这个目标的实验将使我能够评估情境反应和情境结果关联对行为的相对贡献。这些实验将为一项研究计划奠定基础，该计划的重点是询问有关学习和记忆中特定上下文关联性质的问题。

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.