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.

项目摘要和摘要与恐惧相关的压力和焦虑症在全世界数百万人中表现出来，许多人遵循创伤或令人恐惧的经历。虽然这些疾病的症状是众所周知的，但我们的症状不足关于大脑如何编码和修饰恐惧记忆的知识。听觉和上下文如何在过去的几十年中，形成的记忆已经彻底研究了，但是，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参与嗅觉恐惧记忆的处理。我发现了一个离散电路，该电路由神经元组成后中值皮质杏仁核（PMCOA）降至中位前额叶皮层（IL）的额叶分裂。在嗅觉恐惧调节之前使用化学遗传学沉默这一途径会导致恐惧的加强对条件气味的响应。目标1建议确定厌恶嗅觉记忆的阶段处理此电路。为此，我将在获取，合并和灭绝以确定该途径在每个过程中具有的程度。 AIM 2将决定该电路通过获取，合并，检索和扩展的学习气味引起。我将使用纤维光度法直接记录投射IL的PMCOA神经元内的钙活性（PMCOA→IL神经元）确定在厌恶嗅觉记忆的这些不同阶段，该电路激活的激活模式加工。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大脑中组织。