The effect of zolpidem on targeted memory reactivation during sleep

According to the active system consolidation theory, memory consolidation during sleep relies on the reactivation of newly encoded memory representations. This reactivation is orchestrated by the interplay of sleep slow oscillations, spindles, and theta, which are in turn modulated by certain neurotransmitters like GABA to enable long-lasting plastic changes in the memory store. Here we asked whether the GABAergic system and associated changes in sleep oscillations are functionally related to memory reactivation during sleep. We administered the GABA_A agonist zolpidem (10 mg) in a double-blind placebo-controlled study. To specifically focus on the effects on memory reactivation during sleep, we experimentally induced such reactivations by targeted memory reactivation (TMR) with learning-associated reminder cues presented during post-learning slow-wave sleep (SWS). Zolpidem significantly enhanced memory performance with TMR during sleep compared with placebo. Zolpidem also increased the coupling of fast spindles and theta to slow oscillations, although overall the power of slow spindles and theta was reduced compared with placebo. In an uncorrected exploratory analysis, memory performance was associated with slow spindle responses to TMR in the zolpidem condition, whereas it was associated with fast spindle responses in placebo. These findings provide tentative first evidence that GABAergic activity may be functionally implicated in memory reactivation processes during sleep, possibly via its effects on slow oscillations, spindles and theta as well as their interplay.