Cortical Amygdala to Medial Prefrontal Cortex Circuit Control of Olfactory Fear Memories

项目摘要和摘要 与恐惧相关的压力和焦虑症在世界各地数百万人中表现出来，其中许多人 在经历了一次创伤或可怕的经历之后。虽然这些疾病的症状是众所周知的，但我们缺乏 大脑如何编码和修改恐惧记忆的知识并非如此。如何听觉和情境化 在过去的几十年里，人们对记忆的形成进行了深入的研究，然而，对厌恶嗅觉的研究 恐惧记忆相对稀少。这些实验将确定一个新的电路是否参与了 嗅觉恐惧记忆的处理。我发现了一个由神经元组成的离散电路 内侧前额叶皮质(IL)的后内侧杏仁皮质(PmCoA)至边缘下部。 在嗅觉恐惧条件作用之前，使用化学遗传学来沉默这一途径会导致恐惧的加强 对条件气味的反应。目标1建议确定厌恶嗅觉记忆的哪些阶段 这个电路的处理涉及到。要做到这一点，我将在采集、合并和 灭绝，以确定这条途径对每个过程的影响程度。目标2将决定 这一回路是由习得气味的获取、巩固、提取和消亡引起的。我会用纤维的 用光度法直接记录投射IL的PMCoA神经元(PMCoA→IL神经元)内的钙活动 为了确定在厌恶嗅觉记忆的这些不同阶段中该电路的激活模式 正在处理。这些实验可以提供有关嗅觉恐惧记忆的基本信息 在哺乳动物的大脑中组织起来。

Project Summary and Abstract Fear-related stress and anxiety disorders manifest in millions of individuals throughout the world, many following a traumatic or frightening experience. While the symptoms of these disorders are well known, our lack of knowledge of how the brain encodes and modifies fear memories is not. How auditory and contextual memories are formed have been thoroughly studied in the past decades, however, research on aversive olfactory fear memories is relatively sparse. These experiments will determine the involvement of a novel circuit in the processing of olfactory fear memories. I have discovered a discrete circuit consisting of neurons projecting from the posterior medial cortical amygdala (pmCoA) to infralimbic division of the medial prefrontal cortex (IL). Silencing this pathway using chemogenetics prior to olfactory fear conditioning leads to a strengthening of a fear response to a conditioned odor. Aim 1 proposes to determine what phases of aversive olfactory memory processing this circuit is involved in. To do this, I will silence this circuit prior to acquisition, consolidation, and extinction to determine the degree that this pathway has on each process. Aim 2 will determine the activity of this circuit elicited by acquisition, consolidation, retrieval, and extinction of a learned odor. I will use fiber photometry to directly record calcium activity within the pmCoA neurons projecting the IL (pmCoA→IL neurons) to determine patterns of activation of this circuit during these different phases of aversive olfactory memory processing. These experiments could provide fundamental information on how olfactory fear memories are organized in the mammalian brain.