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久的恐惧记忆，持续一生。事实上，与正常的遗忘不同，恐惧记忆可能会随着时间的推移而变得更加强烈。此外，旧的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，与创伤的原始背景不同。恐惧记忆的这三个属性（持久性、潜伏性和泛化性）无疑是焦虑症在社会中如此普遍、对个体造成如此衰弱的主要原因。这里提出的研究是针对大脑如何将经验转化为永久记忆的问题，这种记忆的强度（潜伏期）会增加，并且随着时间的推移变得不那么具体（概括）。我们的假设是，恐惧记忆的持久性、潜伏性和概括性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创伤记忆这些属性。我们提出了3个目的来回答这个假设所提出的问题：1）在整个恐惧网络中，必须在哪里活动才能建立持久的，孵化的和概括的恐惧记忆？为了实现这一目标，我们将研究构成网络的大脑结构之间的联系，并确定哪些投射有助于持久的恐惧。2)在与威胁体验的关系中，这种活动必须在什么时候发生？为了回答这个问题，我们将在特定的时间与创伤相关的相关途径，以确定是否在收购，保留或回忆活动是最重要的恐惧记忆的这些功能。3)导致持久记忆三个属性表达的活动的本质是什么？我们将在单个神经元水平上对网络活动进行成像，以确定是什么样的活动模式引起了恐惧的这些强大属性。

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.