Sleep to forget: Context independent interference with fear during sleep
Wednesday, Oct 17, 2012, 9:00 AM -10:00 AM
, M. MAKAM
, D. KROUGER
, D. COLAS
, L. DE LECEA
, C. H. HELLER
Psychiatry, Stanford Univ., PALO ALTO, CA;
Stanford, Stanford, CA
Extinction therapy, in which a cue associated with a trauma is introduced in a safe environment, is one of the most effective treatments for post-traumatic stress disorder (PTSD). Evidence suggests that extinction is mediated by the formation of a new “safe” memory limiting the therapeutic effect to the environment in which it was generated. Therefore fear responses to previously extinct cues reemerge in novel environments.
Sleep, rather, is a context-free environment during which therapy can be given. We hypothesized that the manipulation of memories during sleep will result in a generalized response to the cue, not limited to any specific environment. We tested this in mice using Pavolvian fear conditioning in which we paired an odor (Amyl acetate) to a footshock. After 24 hours (required for memory consolidation), we reactivated fear memories by applying the conditioned odor during NREM sleep (20 applications within 2 hours). To interrupt fear memories, we injected the protein synthesis inhibitor (Anisomycin) in the basolateral amygdala (BLA), a brain region necessary for memory storage, prior to applying odors. Two control groups were included. Both were injected with the protein synthesis inhibitor, however, one group received a novel odor during sleep that was not associated with a footshock and another control group received odor applications during the wake episodes in the following two hours to determine the specificity of this effect on sleep.
Twenty-four hours later (for all groups), alert mice were placed in a novel environment and exposed to the conditioned odor, and their freezing response to that cue was measured.
We found that while the mice that were injected with the protein synthesis inhibitor and exposed to the control odor during sleep or with the conditioned odor during wake showed similar freezing responses, the mice that received the conditioned odor during sleep showed an attenuated freezing response. These findings demonstrate the concept that sleep is a unique environment that enables the manipulation of specific memories in a context-independent manner.
L. de Lecea:
NARSAD Young investigator award
[Authors]. [Abstract Title]. Program No. XXX.XX. 2012 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2012. Online.
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