PROJECT SUMMARY/ABSTRACT Sleep is crucial for memory consolidation and its benefit is most commonly thought to occur via the reactivation of memories, thereby strengthening the neural infrastructure supporting them. Theoretical accounts of sleep- related consolidation focus on the process by which memories are independently strengthened, but in natural settings individual memories never exist in a vacuum. Importantly, the context in which memories are embedded during encoding governs retrieval and decision making behavior. However, context’s role in consolidation has not been directly explored. The goal of the proposed project is to improve our fundamental understanding of memory processes by developing an empirically-based framework unifying models of context’s effect on memory and models of sleep-related consolidation (Aim 1; Experiments 1–3). Additionally, the framework may support translational interventions to alter memories during sleep. Aim 2 (Experiments 4–5) will attempt to reinstate a suppression context during sleep to effectively weaken memories. This effort will inform future work on alleviating memory-related symptoms in clinical populations suffering from post-traumatic stress disorder. Whereas the proof-of-concept for both aims will be demonstrated in the K99 phase of this award, the R00 phase will serve to enhance the theoretical framework and establish external validity. Both the translational and basic-science arms of this work will continue in parallel throughout my independent career, in which I will use my fully assembled neurocognitive toolkit to explore sleep’s contribution to memory and the neural infrastructure supporting it. The main behavioral manipulation used in this proposal is targeted memory reactivation, the unobtrusive presentation of learning-related stimuli during sleep, thereby enhancing memory. Experiment 1 (K99 phase) tests whether contexts may be reactivated directly and considers the interactions between reactivation-related benefits of individual memories and contexts. Experiment 2 (K99 phase) investigates whether cues for individual memories presented during sleep reactivate the learning context in a manner that propagates to other memories contextually linked together. Experiment 3 (R00 phase) uses functional MRI pattern analysis techniques to reveal whether contexts, individual memories or both are reactivated during natural, undisturbed sleep. Experiment 4 (K99 phase) attempts to embed individual memories in a previously unrelated context during sleep: a reactivated “suppression” context (cued by an odor) will be presented with auditory cues linked to individual memories, hypothetically weakening them during sleep. Experiment 5 (R00 phase) will use a similar technique to try and alleviate distressful intrusive memories following a trauma manipulation in healthy participants. For this project, I have assembled an expert mentorship team for the K99 phase, including leaders in functional MRI pattern ana...