The role of Acetylcholine in Targeted Memory Reactivation in the long-term

Acetylcholine (ACh) is high during wakefulness and REM sleep but reaches a minimum during slow-wave sleep (SWS). Low ACh during SWS is proposed to shift hippocampal networks from an encoding mode toward a consolidation mode, facilitating memory reactivation and hippocampus-to-neocortex information transfer. Accordingly, pharmacologically increasing ACh during SWS impairs declarative memory consolidation. Memory reactivation can be externally manipulated using Targeted Memory Reactivation (TMR), by re-presenting learning-associated cues. Surprisingly, increasing ACh during TMR does not abolish short-term memory benefits after ~40 min of sleep. Our previous work showed that both complete and incomplete reminders stabilize memories after ~40 min of sleep, whereas only incomplete reminders produce long-term stabilization after ~8 h. Here, we tested whether low cholinergic tone is required for the long-term effects of TMR. Participants learned sound-word associations and received either physostigmine or placebo while half of the associations were reactivated using incomplete reminders. Memory was tested after ~8 h of sleep. Preliminary results showed a TMR benefit in the placebo group, while no comparable benefit was observed under physostigmine. However, the TMR × treatment interaction did not reach statistical significance. These findings raise the possibility that low cholinergic tone may contribute to the long-term effects of targeted memory reactivation.