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

皮质杏仁核到内侧前额叶皮层电路控制嗅觉恐惧记忆

基本信息

批准号：
10163070
负责人：
Christopher deSolis
金额：
$ 6.1万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2022-02-25
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10163070
关键词：
Accessory Olfactory Bulbs Address Amygdaloid structure Anxiety Anxiety Disorders Area Auditory Behavioral Blood Brain Brain region Calcium Cells Clozapine Cues Data Dependovirus Detection Disease Emotional Environment Exhibits Extinction (Psychology)FOS gene Fiber Fright Gasoline Individual Injections Instinct Knowledge Learning Maintenance Medial Memory Modeling Neurobiology Neurons Odors Olfactory Pathways Oxides Pathway interactions Pattern Phase Photometry Prefrontal Cortex Process Research Research Proposals Retrieval Role Route Rubber Sensory Signal Transduction Simplexvirus Smell Perception Structure Symptoms System Tactile Temporal Lobe Testing Time Update Viral Visual anxiety-related disorders avoidance behavior base behavioral response combinatorial conditioned fear conditioning designer receptors exclusively activated by designer drugs education pathway experience experimental study fascinate fear memory insight memory process network models neural circuit neurobiological mechanism novel olfactory bulb olfactory sensory neurons response sensor stress related disorder therapeutic development

项目摘要

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.

项目概要和摘要全世界有数百万人患有与恐惧相关的压力和焦虑症，其中许多人尽管这些疾病的症状众所周知，但我们却缺乏。大脑如何编码和修改恐惧记忆的知识并不那么听觉和情境。记忆的形成在过去的几十年里已经得到了深入的研究，然而，对厌恶嗅觉的研究恐惧记忆相对稀疏。这些实验将确定新电路是否参与其中。我发现了一个由神经元投射的离散电路。后内侧皮质杏仁核 (pmCoA) 到内侧前额叶皮质 (IL) 的边缘下部分。在嗅觉恐惧调节之前使用化学遗传学沉默该通路会导致恐惧的加强对条件气味的反应目标 1 建议确定厌恶性嗅觉记忆的哪个阶段。处理此电路所涉及的内容。为此，我将在采集、合并和处理之前使此电路静音目的 2 将确定该路径对每个过程的活性。这个回路是由习得的气味的获取、巩固、恢复和消除引起的，我将使用纤维。光度测定法直接记录投射 IL 的 pmCoA 神经元内的钙活动（pmCoA→IL 神经元）确定该电路在厌恶嗅觉记忆的不同阶段的激活模式这些实验可以提供有关嗅觉恐惧记忆如何形成的基本信息。在哺乳动物的大脑中组织起来。