Manipulating the consolidation of fear memories during sleep

操纵睡眠期间恐惧记忆的巩固

• 批准号: 8256478
• 负责人: Katherina Hauner
• 金额: $ 4.84万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-12-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8256478
• 关键词: Affect; Afferent Neurons; Algorithms; Amygdaloid structure; Anxiety; Anxiety Disorders; Area; Brain; Characteristics; Clinical; Collection; Complement; Cues; Data; Emotional; Emotions; Episodic memory; Event; Face; Fellowship; Fright; Functional Magnetic Resonance Imaging; Goals; Image Analysis; Individual; Intervention; Laboratories; Lead; Learning; Limbic System; Measures; Mediating; Memory; Mental disorders; Methods; Napping; National Institute of Mental Health; National Research Service Awards; Nature; Neurosciences; Odors; Pattern; Phase; Physiological; Post-Traumatic Stress Disorders; Postdoctoral Individual National Research Service Award; Process; Regulation; Research; Research Personnel; Respiration; Retrieval; Role; Scanning; Shock; Sleep; Smell Perception; Stimulus; Symptoms; Synapses; System; Techniques; Therapeutic Intervention; Training; United States National Institutes of Health; Universities; Wakefulness; Work; awake; base; classical conditioning; clinically relevant; conditioned fear; conditioning; critical period; design; experience; innovation; medical schools; novel; relating to nervous system; response

DESCRIPTION (provided by applicant): This is a request to the NIH/NIMH for an Individual NRSA Postdoctoral Fellowship (F32) Award for Dr. Katherina Hauner, Research Fellow in the laboratory of Dr. Jay Gottfried, at Northwestern University Feinberg School of Medicine. Of all mental illnesses, anxiety disorders are the most prevalent. Treatment involves remodeling fear memories via a process of consolidation. The most critical period for memory consolidation is during sleep- particularly for emotional memory, such as fear. Moreover, symptoms of anxiety disorders (such as PTSD) predict impaired fear memory consolidation during sleep. Thus, the goal of the proposed research is to determine how consolidation of fear memories can be selectively modulated during sleep. This objective marks a novel extension of the applicant's previous work on the neural substrates of fear after exposure therapy. The proposed research will incorporate groundbreaking techniques that use olfactory contextual cues to modulate memory during sleep. While sleep is known to promote consolidation of fear memories, it is unknown if consolidation can be selectively manipulated to modulate fear memories. Critically, the decision to use odor stimuli as memory modulators is based on the intimate anatomical and functional connections between olfactory and limbic systems-olfactory sensory neurons are only two synapses removed from brain areas involved in emotion and learning. Prior research from the sponsor's lab has highlighted involvement of amygdala and orbitofrontal cortex (OFC) in olfactory-based fear conditioning. Moreover, there is recent evidence to suggest that odors have privileged access to brain networks during sleep, and that non-emotional, episodic memories can be manipulated by using odors as contextual cues. The central hypothesis of the proposed project is that an odor cue originally presented in the context of a feared stimulus-then continuously re-presented during sleep by itself-will destabilize the strength of the fear memory. This effect will be compared to a control condition in which the contextual odor cue is not re- presented during sleep. Fear responses will be measured using physiological recordings and fMRI. Using pattern-based (multivariate) imaging analyses, we predict that fMRI signatures of fear responses in amygdala and OFC at retrieval will show reduced pattern coherence to fear responses established at training, for feared stimuli in the odorant context that was also re-presented during sleep. Findings will have broad clinical relevance, as the proposed methods could serve to complement and accelerate existing therapy. The proposed research will require the applicant to complete new training in classical conditioning, physiological assessment of fear, olfaction, and advanced fMRI analysis-all highly relevant for her future research endeavors. The translational nature of this project will put the applicant firmly on the path toward becoming an independent investigator who applies neuroscience approaches to inspire novel clinical interventions.

描述（由申请人提供）：这是向NIH/NIMH提出的申请，申请为西北大学范伯格医学院Jay Gottfried博士实验室的研究员Katherina Hauner博士颁发个人NRSA博士后奖学金（F32）。 在所有精神疾病中，焦虑症是最普遍的。治疗包括通过巩固过程重塑恐惧记忆。记忆巩固最关键的时期是在睡眠期间-特别是对于情绪记忆，如恐惧。此外，焦虑症（如PTSD）的症状预示着睡眠期间恐惧记忆巩固受损。因此，这项研究的目的是确定如何在睡眠期间选择性地调节恐惧记忆的巩固。这一目标标志着申请人先前关于暴露疗法后恐惧的神经基质的工作的新扩展。 拟议中的研究将采用突破性的技术，使用嗅觉上下文线索来调节睡眠期间的记忆。虽然已知睡眠可以促进恐惧记忆的巩固，但不知道是否可以选择性地操纵巩固来调节恐惧记忆。关键的是，使用气味刺激作为记忆调节器的决定是基于嗅觉系统和边缘系统之间密切的解剖学和功能联系嗅觉感觉神经元只是与涉及情感和学习的大脑区域分离的两个突触。赞助者实验室先前的研究强调了杏仁核和眶额皮质（OFC）参与基于嗅觉的恐惧条件反射。此外，最近有证据表明，气味在睡眠期间有特权进入大脑网络，并且可以通过使用气味作为上下文线索来操纵非情绪的情景记忆。 该项目的核心假设是，最初在恐惧刺激的背景下呈现的气味线索，然后在睡眠中不断地重新呈现，将破坏恐惧记忆的强度。将该效果与对照条件进行比较，其中在睡眠期间不重新呈现背景气味线索。恐惧反应将使用生理记录和功能磁共振成像测量。使用模式为基础的（多变量）成像分析，我们预测，功能磁共振成像签名的恐惧反应在杏仁核和眶额皮层在检索将显示减少模式的连贯性建立在训练的恐惧反应，恐惧刺激的气味的背景下，也在睡眠中重新提出。研究结果将具有广泛的临床意义，因为所提出的方法可以补充和加速现有的治疗。拟议的研究将要求申请人完成经典条件反射，恐惧的生理评估，嗅觉和高级功能磁共振成像分析的新培训-所有这些都与她未来的研究工作高度相关。该项目的翻译性质将使申请人坚定地走上成为独立研究者的道路，他们应用神经科学方法来激发新的临床干预措施。