Memory Consolidation Is Linked to Spindle-Mediated Information Processing during Sleep

How are brief encounters transformed into lasting memories? Previous research has established the role of non-rapid eye movement (NREM) sleep, along with its electrophysiological signatures of slow oscillations (SOs) and spindles, for memory consolidation 1Marshall L. Helgadóttir H. Mölle M. Born J. Boosting slow oscillations during sleep potentiates memory.Nature. 2006; 444: 610-613Crossref PubMed Scopus (1272) Google Scholar, 2Mednick S.C. McDevitt E.A. Walsh J.K. Wamsley E. Paulus M. Kanady J.C. Drummond S.P.A. The critical role of sleep spindles in hippocampal-dependent memory: a pharmacology study.J. Neurosci. 2013; 33: 4494-4504Crossref PubMed Scopus (185) Google Scholar, 3Ngo H.-V.V. Martinetz T. Born J. Mölle M. Auditory closed-loop stimulation of the sleep slow oscillation enhances memory.Neuron. 2013; 78: 545-553Abstract Full Text Full Text PDF PubMed Scopus (454) Google Scholar, 4Ngo H.-V.V. Miedema A. Faude I. Martinetz T. Mölle M. Born J. Driving sleep slow oscillations by auditory closed-loop stimulation-a self-limiting process.J. Neurosci. 2015; 35: 6630-6638Crossref PubMed Scopus (120) Google Scholar. In related work, experimental manipulations have demonstrated that NREM sleep provides a window of opportunity to selectively strengthen particular memory traces via the delivery of auditory cues 5Cairney S.A. Sobczak J.M. Lindsay S. Gaskell M.G. Mechanisms of memory retrieval in slow-wave sleep.Sleep. 2017; 40https://doi.org/10.1093/sleep/zsx114Crossref PubMed Scopus (11) Google Scholar, 6Fuentemilla L. Miró J. Ripollés P. Vilà-Balló A. Juncadella M. Castañer S. Salord N. Monasterio C. Falip M. Rodríguez-Fornells A. Hippocampus-dependent strengthening of targeted memories via reactivation during sleep in humans.Curr. Biol. 2013; 23: 1769-1775Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar, 7Rudoy J.D. Voss J.L. Westerberg C.E. Paller K.A. Strengthening individual memories by reactivating them during sleep.Science. 2009; 326: 1079Crossref PubMed Scopus (325) Google Scholar, 8Oudiette D. Antony J.W. Creery J.D. Paller K.A. The role of memory reactivation during wakefulness and sleep in determining which memories endure.J. Neurosci. 2013; 33: 6672-6678Crossref PubMed Scopus (123) Google Scholar, 9Schreiner T. Rasch B. Boosting vocabulary learning by verbal cueing during sleep.Cereb. Cortex. 2015; 25: 4169-4179Crossref PubMed Scopus (103) Google Scholar, 10Cousins J.N. El-Deredy W. Parkes L.M. Hennies N. Lewis P.A. Cued reactivation of motor learning during sleep leads to overnight changes in functional brain activity and connectivity.PLoS Biol. 2016; 14: e1002451Crossref PubMed Scopus (45) Google Scholar, a procedure known as targeted memory reactivation (TMR). It has remained unclear, however, whether TMR triggers the brain’s endogenous consolidation mechanisms (linked to SOs and/or spindles) and whether those mechanisms in turn mediate effective processing of mnemonic information. We devised a novel paradigm in which associative memories (adjective-object and adjective-scene pairs) were selectively cued during a post-learning nap, successfully stabilizing next-day retention relative to non-cued memories. First, we found that, compared to novel control adjectives, memory cues evoked an increase in fast spindles. Critically, during the time window of cue-induced spindle activity, the memory category linked to the verbal cue (object or scene) could be reliably decoded, with the fidelity of this decoding predicting the behavioral consolidation benefits of TMR. These results provide correlative evidence for an information processing role of sleep spindles in service of memory consolidation.