Ion Channel Plasticity and Aversive Memory Priming

项目摘要 厌恶记忆的获得和持续是基于恐惧的障碍的中心组成部分，例如 创伤后应激障碍。巴甫洛夫式的恐惧条件作用使用中性线索来预测 令人厌恶的事件，通常是轻微的电击。在球杆与电击配对后，生物体将展示 与表达恐惧一致的行为，我们测量这些行为是为了推断学习已经 已经发生了。这种形式的学习被广泛用作研究基于恐惧的记忆是如何形成的模型系统 恐惧条件作用的研究已经产生了关于细胞和分子的详细知识 恐惧记忆形成所必需的机制。这项工作的大部分都使用了培训程序，在这些程序中 记忆是在与其他受控经验隔离的情况下获得的。然而，记忆通常不是 在与其他经验隔离的情况下获得的，而且实际上会受到先前经验的影响。作为一种 例如，我们之前的研究表明，先前的恐惧条件反射可以促进新的 当出现另一个提示时的恐惧，并伴随着几个小时或几天后的震惊。鉴于其深远的影响 对于以前的经验，确定过去的经验影响以后学习的机制对于 我们对学习和记忆的理解。我们的长期目标是了解神经生物学 允许先前的恐惧条件反射来改变随后的恐惧学习的机制。这项提案的目标是 是为了确定特定离子通道蛋白的表达是否需要改变 初始体验启动后续学习的能力，或初始体验的记忆形成，或两者兼而有之 流程。我们的假设是，含有1-β亚基的钠通道表达的变化， 和Kv4.2钾通道，在未来学习的启动中起着特定的作用，但不是必需的 记忆的形成或恐惧行为的表达。为了实现这一目标，我们将结合行为 研究，通过蛋白质和RNA表达分析，以及位点特异性RNA干扰。在具体目标1中，我们 将测试最初的恐惧条件作用试验启动以后学习的能力是否取决于改变的表达 杏仁基底外侧核中含有1-β亚基的钠通道。在具体目标2中，我们将测试 Kv4.2钾通道的参与。这个项目的重点是描述神经机制。 这使得先前的经验成为未来记忆形成的主要因素。在这里获得的基本信息具有一定的影响 对于基于恐惧的障碍的病因学，并最终可能为他们的治疗开辟新的途径。

Project Summary The acquisition and persistence of an aversive memory is a central component of fear-based disorders such as post-traumatic stress disorder. Pavlovian fear conditioning uses neutral cues that predict the occurrence of an aversive event, typically a mild electric shock. After pairings of the cue with shock, organisms will exhibit behaviors that are consistent with the expression of fear, and which we measure to infer that learning has taken place. This form of learning is widely used as a model system for studying how fear-based memories are formed, and the study of fear conditioning has yielded detailed knowledge regarding the cellular and molecular mechanisms necessary for fear memory formation. Much of this work has used training procedures in which memories were acquired in isolation from other controlled experiences. However, memories are not normally acquired in isolation from other experiences, and in fact can be influenced by prior experiences. As an example, our previous studies have showed that prior fear conditioning can facilitate the acquisition of new fears when another cue is presented and paired with shock hours or days later. Given the profound influence of prior experience, identifying the mechanisms by which past experience impacts later learning is essential to our understanding of learning and memory. Our long-term goal is to understand the neurobiological mechanisms that allow prior fear conditioning to alter subsequent fear learning. The objective in this proposal is to determine whether or not changes in the expression of specific ion channel proteins are required for the ability of the initial experience to prime subsequent learning, memory formation for an initial experience, or both processes. Our hypothesis is that changes in expression of sodium channels containing the 1-beta subunit, and Kv4.2 potassium channels, play a specific role in the priming of future learning, but are not required for memory formation or the expression of fear behavior. To achieve this objective, we will combine behavioral studies, with protein and RNA expression analysis, and site-specific RNA interference. In specific Aim 1, we will test if the ability of an initial fear conditioning trial to prime later learning depends on altered expression of sodium channels containing the 1-beta subunit in the basolateral amygdala. In specific Aim 2, we will test the involvement of the Kv4.2 potassium channel. This project is focused on describing the neural mechanisms that allow prior experience prime future memory formation. The basic information gained here has implications for the etiology of fear-based disorders and ultimately may open up new avenues for their treatment.