Institute of Medical Psychology and Behavioural Neurobiology, University of Tübingen, 72076 Tübingen, Germany.
Graduate Training Centre of Neuroscience, International Max Planck Research School, University of Tübingen, 72076 Tübingen, Germany.
Learn Mem. 2021 Aug 16;28(9):307-318. doi: 10.1101/lm.052787.120. Print 2021 Sep.
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 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.
根据活跃系统巩固理论，睡眠期间的记忆巩固依赖于新编码的记忆表征的重新激活。这种再激活是由睡眠慢波、纺锤波和θ波的相互作用协调的，而这些波又受到 GABA 等特定神经递质的调制，从而使记忆库中产生持久的可塑性变化。在这里，我们想知道 GABA 能系统及其相关的睡眠振荡变化是否与睡眠期间的记忆再激活有功能上的关系。我们在一项双盲安慰剂对照研究中给予 GABA 激动剂唑吡坦（10 毫克）。为了专门关注睡眠期间记忆再激活的影响，我们通过在学习后慢波睡眠（SWS）期间呈现与学习相关的提示线索来进行有针对性的记忆再激活（TMR），从而实验性地诱导这种再激活。与安慰剂相比，唑吡坦在睡眠期间进行 TMR 时显著提高了记忆表现。唑吡坦还增加了快纺锤波和θ波与慢波的耦合，尽管与安慰剂相比，慢纺锤波和θ波的整体功率降低。在未经校正的探索性分析中，记忆表现与唑吡坦条件下 TMR 的慢纺锤波反应相关，而与安慰剂条件下的快纺锤波反应相关。这些发现提供了初步的证据，表明 GABA 能活性可能在睡眠期间的记忆再激活过程中具有功能相关性，可能是通过其对慢波、纺锤波和θ波及其相互作用的影响。
