Odor-Induced Reactivation and Reorganization of Fear Memory in the Sleeping Human Brain

Project: Research project

Project Details

Description

Since the landmark studies of Pavlov, neuroscience research on associative learning has focused on understanding how fear memories are stored in the brain, and of equal importance, how those fear memories can be eradicated from the brain. Experimental models of fear “extinction” have begun to shed light on the mechanisms by which humans and other animals dampen their fear to sensory triggers that no longer portend threat. Clarifying the neural processes that regulate emotional memory storage holds far-reaching ramifications for psychiatric disorders involving pathological fear and anxiety, which are thought to arise from a dysregulation of fear extinction mechanisms. Our research proposal is designed to test the innovative hypothesis that sleep offers a unique window in which fear memories can be targeted for extinction.

That we spend so much time asleep is evidence that sleep holds important physiological relevance. The last few years have witnessed a dramatic upsurge of data suggesting that one key role of sleep is to strengthen memories of events encountered in the waking state. Recent studies intriguingly indicate that memories can be selectively targeted and reactivated in sleep via presentation of a sound or smell previously experienced in the wake state during training. These experimental manipulations offer a dramatic opportunity for determining which memories endure and which memories fade. In our new work, we found that odor cues delivered during sleep can weaken fear memories in a stimulus-specific manner, with critical involvement of limbic emotional brain areas in the amygdala and hippocampus. Although these results provide new insights into sleep regulation of fear memory and extinction, the key mechanisms underlying this process remain unknown. In particular, the widespread assumption that a “replay” of the original memory during sleep is essential for subsequent modulation has not been directly demonstrated in the human brain.

The central goal of this research proposal is to identify a neural signature of fear memory replay during sleep, and to determine whether extinction of these replayed memories during sleep predicts fear extinction in the waking state. Here, healthy human subjects will undergo functional magnetic resonance imaging (fMRI) while taking part in olfactory fear conditioning. In an initial training session while awake, subjects will learn to associate a face picture with mild electric shock while an odor is simultaneously presented. Next, subjects will take a nap in the fMRI scanner, and when subjects enter slow-wave sleep, an odor will be re-delivered in order to trigger “replay” of the learned associations between that odor, the face, and fear. The use of fMRI pattern-based analysis techniques will enable us to confirm that the odor triggers stimulus-specific reactivation (replay) of the original fear event, and importantly, also confirm that the fear memory progressively weakens with repeated odor-induced replay during sleep, consistent with extinction. The ability to tag specific events for transformation during sleep will highlight new opportunities for enhancing beneficial memories and disrupting maladaptive memories, with particular relevance for diseases such as post-traumatic stress disorder, specific phobias, and other anxiety disorders commonly associated with environmental triggers.
StatusFinished
Effective start/end date9/15/159/14/18

Funding

  • Brain & Behavior Research Foundation (23272)

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