Anterograde Amnesia for Contextual Fear

描述（由申请人提供）：威胁或厌恶的经历可以产生持续一生的持久恐惧记忆。事实上，随着时间的推移，恐惧记忆可能会随着时间的推移而变得更加强烈，而不是正常的遗忘。此外，旧恐惧记忆的触发因素变得不那么具体；随着时间的推移，恐惧变得越来越普遍，与创伤的原始环境不同。恐惧记忆的这三个特征（持久、孵化和概括）无疑是焦虑症在社会上如此普遍、患者如此虚弱的主要原因。这里提出的研究是针对大脑如何将经历转化为永久记忆的问题，这种记忆在强度上增加（潜伏期），随着时间的推移变得不那么具体（泛化）。我们的假设是，恐惧记忆的持久，孕育和概括属性需要几个神经结构的协调活动，正是这种协调活动赋予了创伤性记忆这些属性。我们提出了三个目标来回答这一假设提出的问题：1)在整个恐惧网络中，必须发生活动才能建立持久，孵化和概括的恐惧记忆？为了实现这一目标，我们将关闭构成网络的大脑结构之间的连接，并确定哪些投射有助于持久的恐惧。2)与威胁体验相关的这种活动在什么时候必须发生？为了回答这个问题，我们将在特定时间关闭与创伤相关的相关通路，以确定获取、保留或回忆期间的活动是否对恐惧记忆的这些特征最重要。3)导致持久记忆的三个属性表达的活动的性质是什么？我们将在单个神经元水平上对网络活动进行成像，以确定哪些活动模式会产生这些强大的恐惧属性。

DESCRIPTION (provided by applicant): Threatening or aversive experiences can produce enduring fear memories that last a lifetime. Indeed, rather than normal forgetting, fear memories may incubate becoming more intense as time passes. In addition, the triggers for old fear memories become less specific; as time passes fear becomes increasingly generalized to conditions that differ from the original context of the trauma. These three attributes of fear memory (enduring, incubating and generalizing) are no doubt major contributors to the fact that anxiety disorders are so prevalent in society and so debilitating to the individuals that suffer from them. The research proposed here is directed at the question of how the brain translates an experience into a permanent memory that increases in intensity (incubation) and becomes less specific over time (generalization). Our hypothesis is that, the enduring, incubating and generalizing attributes of fear memory require coordinated activity in several neural structures and it is this coordinated activity that gives traumatic memories these attributes. We propose 3 aims to answer the questions raised by this hypothesis: 1) Where in the overall fear network must activity occur to establish enduring, incubating and generalizing fear memory? To achieve this we will inactivate connections between the brain structures that comprise the network and determine which of these projections contribute to enduring fear. 2) When, in relationship to the threatening experience, must this activity occur? To answer this question we will inactivate the relevant pathways at specific times in relation to the trauma to determine if activity during acquisition, retention or recall is most important for these features of fear memory. 3) What is the nature of the activity that leads to the expression of the 3 attributes of enduring memory? We will image network activity at the single neuron level to determine what patterns of activity give rise to these powerful attributes of fear.