Episodic memories undergo qualitative changes with time, but little is known about how different aspects of memory are affected. Different types of information in a memory, such as perceptual detail, and central themes, may be lost at different rates. In patients with medial temporal lobe damage, memory for perceptual details is severely impaired, while memory for central details is relatively spared. Given the sensitivity of memory to loss of details, the present study sought to investigate factors that mediate the forgetting of different types of information from naturalistic episodic memories in young healthy adults. The study investigated (1) time-dependent loss of “central” and “peripheral” details from episodic memories, (2) the effectiveness of cuing with reminders to reinstate memory details, and (3) the role of retrieval in preventing forgetting. Over the course of 7 d, memory for naturalistic events (film clips) underwent a time-dependent loss of peripheral details, while memory for central details (the core or gist of events) showed significantly less loss. Giving brief reminders of the clips just before retrieval reinstated memory for peripheral details, suggesting that loss of details is not always permanent, and may reflect both a storage and retrieval deficit. Furthermore, retrieving a memory shortly after it was encoded prevented loss of both central and peripheral details, thereby promoting retention over time. We consider the implications of these results for behavioral and neurobiological models of retention and forgetting.

After acquisition, memories associated with contextual fear conditioning pass through a labile phase, in which they are vulnerable to hippocampal lesions, to a more stable state, via consolidation, in which they engage extrahippocampal structures and are resistant to such disruption. The process is accompanied by changes in the form of the memory from being context-specific to context-general. However, when revived by a reminder, stable memories once again become labile and susceptible to hippocampal disruption, and memory reconsolidation is needed to stabilize them. This study addressed two questions with respect to this reconsolidation phenomenon: (1) How do reminders reinstate a hippocampally dependent memory trace? (2) As the memory changes from a stable to a labile state after a reminder, does its form remain invariant, or does it also change? Using contextual manipulations at retrieval in a test of contextual fear conditioning, we showed that when the fear-conditioning environment served as a reminder, the reinstated memory regained its context specificity and, as a result, became vulnerable again to the effects of hippocampal lesions. By comparison, exposure to a different environment during the reminder session reinstated a version of the original memory that was dependent primarily on general features of the original context and, consequently, was less affected by hippocampal lesions. These findings, which relate loss of reactivated memories after hippocampal destruction (or inactivation) to changes in memory representation, are interpreted as consistent with the transformation hypothesis of memory processing.

Although the transcription factor CREB has been widely implicated in memory, whether it is sufficient to produce spatial memory under conditions that do not normally support memory formation in mammals is unknown. We found that locally and acutely increasing CREB levels in the dorsal hippocampus using viral vectors is sufficient to induce robust spatial memory in two conditions that do not normally support spatial memory, weakly trained wild-type (WT) mice and strongly trained mutant mice with a brain-wide disruption of CREB function. Together with previous results, these findings indicate that CREB is both necessary and sufficient for spatial memory formation, and highlight its pivotal role in the hippocampal molecular machinery underlying the formation of spatial memory.