The functional role of labilization and reconsolidation for memory formation during sleep and wakefulness
Human Cognitive and Systems Neuroscience
Final Report Abstract
This was a collaborative project in a special funding scheme with a German partner (funded by the DFG) and an Argentinian partner (funded by CONICET/MINCyT). In this way, the project allowed for an intense academic exchange between the two applicants and their group members and resulted in new advances in the field of memory and sleep. The core hypothesis of the project was that the known effects of memory reactivation during sleep and wakefulness rely on processes of labilization and reconsolidation and that these processes serve a functional role for long-term memory formation. In a series of experiments, we applied targeted memory reactivation (TMR) with learning-associated sound cues to directly manipulate memory reactivation during sleep and wakefulness and to examine the underlying neurophysiological mechanisms. The findings from this project show that only incomplete reminder cues, which trigger memory labilization in the wake state, induce memory stabilization for the longterm when applied during sleep. Complete reminders, on the other hand, which do not trigger memory labilization in the wake state, only resulted in short-term but not in long-term stabilization. These findings suggest that transient memory labilization may be a key mechanism underlying the beneficial effects of memory reactivation during sleep, possibly allowing for the integration of new memories into neocortical networks for long-term storage. Further experiments showed that this process of reactivation with incomplete reminder cues is dependent on GABAergic activity during sleep, with pharmacologically increasing GABAergic activity resulting in even stronger long-term memory stabilization. Preliminary data further suggest that these reactivation/stabilization processes may not depend on low cholinergic tone during sleep, although there were a few unexpected findings that still need to be scrutinized before making any conclusions. A further set of experiments showed that the reactivation with incomplete reminder cues is equally effective during slow wave sleep (SWS) and sleep stage 2 (S2). Thus, our data provide novel evidence that the mechanisms underlying memory reactivation during sleep may be similarly effective during SWS and S2, which was an unexpected finding that should be further examined. Finally, we observed that sleep accelerates the re-stabilization of memories that had been labilized during prior wakefulness. While re-stabilization took several hours during wakefulness, it was already achieved after only 40 min of sleep. Together, the findings from this project advance our understanding of the mechanisms of memory formation during sleep, indicating that labilization and re-stabilization of the underlying memory traces play a functional role in this process. We believe that this knowledge will advance the development of new technologies to facilitate or change memories in therapeutic and educational settings.
Publications
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Sleep accelerates re-stabilization of human declarative memories. Neurobiology of Learning and Memory, 162, 1-8.
Moyano, Malen D.; Diekelmann, Susanne; Pedreira, María E. & Forcato, Cecilia
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Reactivation during sleep with incomplete reminder cues rather than complete ones stabilizes long-term memory in humans. Communications Biology, 3(1).
Forcato, Cecilia; Klinzing, Jens G.; Carbone, Julia; Radloff, Michael; Weber, Frederik D.; Born, Jan & Diekelmann, Susanne
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The effect of zolpidem on targeted memory reactivation during sleep. Learning & Memory, 28(9), 307-318.
Carbone, Julia; Bibián, Carlos; Reischl, Patrick; Born, Jan; Forcato, Cecilia & Diekelmann, Susanne
