Long-term discrimination and generalization of fear and extinction memories during sleep

点击翻译按钮获取中文摘要

Learning when to fear, i.e., when a stimulus signals danger and when not, is essential to an individual’s survival. To behave adaptively in a changing environment where predictive cues are unlikely to occur in exactly the same way, learnt associations need to be generalized to future similar situations. Accumulating evidence indicates that sleep supports generalization of neutral information, but less is known about sleep’s role in generalizing danger and safety information. We hypothesize that sleep is essentially involved in the gradual formation of danger and safety schemas as an important prerequisite that enables the generalization to novel situations. In parallel mice and human studies, we will determine the impact of sleep on long-term discrimination and generalization of conditioned fear and extinction memories (Aim 1). We will characterize mechanisms and neural correlates of fear memory processing during sleep in mice using targeted memory reactivation (Aim 2). Finally, we aim to modulate sleep-dependent long-term fear discrimination and generalization in healthy humans using targeted memory reactivation (Aim 3). This project will increase our mechanistic understanding of sleep’s function in discrimination and generalization of fear and extinction memories, and also guide translation to clinical research questions in the next funding period. 103