Manipulating the consolidation of fear memories during sleep

操纵睡眠期间恐惧记忆的巩固

• 批准号: 8392679
• 负责人: Katherina Hauner
• 金额: $ 2.91万
• 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 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8392679
• 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 申请为西北大学 Feinberg 医学院 Jay Gottfried 博士实验室研究员 Katherina Hauner 博士颁发个人 NRSA 博士后奖学金 (F32) 的请求。 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。记忆巩固的最关键时期是睡眠期间，尤其是情绪记忆，例如恐惧。此外，焦虑症（如创伤后应激障碍）的症状预示着睡眠期间恐惧记忆巩固受损。因此，拟议研究的目标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之前关于暴露疗法后恐惧的神经基质的工作的新颖延伸。 拟议的研究将采用突破性技术，利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，但尚不清楚是否可以选择性地操纵巩固来调节恐惧记忆。至关重要的是，使用气味刺激作为记忆调节剂的决定是基于嗅觉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从涉及情感和学习的大脑区域中移除的两个突触。赞助商实验室之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调节。此外，最近有证据表明，气味在睡眠期间可以优先进入大脑网络，并且可以通过使用气味作为情境线索来操纵非情感的情景记忆。 该项目的中心假设是，最初在恐惧刺激的背景下出现的气味提示，然后在睡眠期间不断重新出现，会破坏恐惧记忆的强度。该效果将与控制条件进行比较，在控制条件下，在睡眠期间不再现背景气味提示。将使用生理记录和功能磁共振成像来测量恐惧反应。使用基于模式的（多变量）成像分析，我们预测杏仁核和 OFC 检索时恐惧反应的 fMRI 特征将显示出与训练时建立的恐惧反应的模式一致性降低，因为气味环境中的恐惧刺激也在睡眠期间重现。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、恐惧生理评估、嗅觉和高级功能磁共振成像分析方面的新培训——所有这些都与她未来的研究工作高度相关。该项目的转化性质将使申请人坚定地走上成为一名独立研究者的道路，应用神经科学方法来激发新颖的临床干预措施。