Anterograde Amnesia for Contextual Fear

描述(由申请人提供)：威胁性或厌恶的经历会产生持久的恐惧记忆，持续一生。事实上，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，出现的情况与创伤的原始背景不同。恐惧记忆的这三个属性(持久、孕育和泛化)无疑是导致焦虑症在社会中如此普遍的事实的主要原因，并因此使患有焦虑症的人变得虚弱。这里提出的研究针对的是大脑如何将经验转化为永久记忆，随着时间的推移，这种记忆的强度会增加(潜伏期)，而变得不那么具体(概括)。我们的假设是，恐惧记忆的持久、孵化和泛化属性需要几个神经结构中的协调活动，正是这种协调活动赋予了创伤记忆这些属性。我们提出3个目标来回答这一假说提出的问题：1)在整个恐惧网络中，必须在哪里发生活动才能建立持久的、孵化和概括的恐惧记忆？为了实现这一点，我们将停用组成网络的大脑结构之间的连接，并确定这些投射中的哪些有助于持久的恐惧。2)与威胁性体验相关，这种活动必须在什么时候发生？为了回答这个问题，我们将在与创伤相关的特定时间使相关通路失活，以确定在获得、保持或回忆过程中的活动对恐惧记忆的这些特征是最重要的。3)导致持久记忆三个属性表达的活动的性质是什么？我们将描绘单个神经元水平上的网络活动，以确定哪些活动模式会引发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.