Sleep is critically involved in strengthening memories. However, our understanding of the morphological changes underlying this process is still emerging. Recent studies suggest that specific subsets of dendritic spines are strengthened during sleep in specific neurons involved in recent learning. Contextual memories associated with traumatic experiences are involved in post-traumatic stress disorder (PTSD) and represent recent learning that may be strengthened during sleep. We tested the hypothesis that dendritic spines encoding contextual fear memories are selectively impacted by sleep deprivation. Furthermore, we tested how sleep deprivation after initial fear learning impacts dendritic spines following re-exposure to fear conditioning. We used ArcCreERT2 mice to visualize neurons that encode contextual fear learning (Arc+ neurons), and concomitantly labeled neurons that did not encode contextual fear learning (Arc- neurons). Dendritic branches of Arc + and Arc- neurons were sampled using confocal imaging to assess spine densities using three-dimensional image analysis from either sleep deprived (SD) or control mice allowed to sleep normally. Mushroom spines in Arc+ branches displayed decreased density in SD mice. In comparison, no changes were observed in dendritic spines from Arc- branches. When animals were re-exposed to contextual fear conditioning 4 weeks later, we observed lower density of mushroom spines in both Arc + and Arc- branches, as well as lower density of thin spines in Arc- branches in mice that were SD following the initial fear conditioning trial. Our findings indicate that sleep deprivation following exposure to contextual fear conditioning selectively impacts dendritic spines in neurons that recently encoded fear memory, both initially and following later re-exposure. SD following a traumatic experience thus may represent a promising strategy for modifying the strength of contextual memories associated with trauma and PTSD.
Tennin et al. (Tue,) studied this question.