Post-conditioning sleep deprivation facilitates delay and trace fear memory extinction.

Trace and delay auditory fear conditioning involve different memory association strategies based on working memory involvement; however, their differences in long-term processing through sleep and extinction training remain unclear. While females often exhibit more persistent fear, complicating psychiatric treatment, most studies have primarily focused on how sleep affects initial recall in male mice. We investigated the three-way interaction between tests (trace vs. delay), sleep states, and sex during initial recall, extinction, and post-extinction remote recall. A six-hour post-conditioning sleep deprivation (SD) did not affect freezing behavior during the following day's extinction training of delay fear memory. However, during post-extinction remote recall of delay fear memory, SD prevented spontaneous recovery in males and reduced persistent freezing in females. In contrast, SD rapidly facilitated extinction of trace fear memory. In summary, SD enhances extinction both in the short-term and long-term, depending on the conditioning protocol. These findings highlight the importance of long-term assessments to explore interactions among emotional memory, sleep, and sex differences, with implications for individualized mechanisms underlying post-traumatic stress disorder (PTSD) and its treatments.