Why the same cue can either loosen or lock a memory
The key idea is that a memory is not fixed once stored. Recalling it, or being reminded of it by a cue, can briefly return it to a changeable state before it is stored again. What happens during that window depends heavily on what the brain is doing at the time. In waking, the brain is actively taking in new information, so a reactivated memory is exposed to whatever arrives next. During slow-wave sleep, the brain is not encoding much new experience, and the same reminder appears to push the memory toward stabilization instead [4].
This is why the wake-versus-sleep comparison is not just a difference in degree. The two states seem to place a reactivated memory on different trajectories: one toward vulnerability, the other toward protection. The 2011 study framed this as memories being 'labile or stable' depending on the state in which reactivation occurs, and its interference test supported that framing [4].
What interference actually does to a reactivated memory
Interference means learning something new that competes with, or overlaps, what you already know. In the reactivation study, participants' memories were reactivated and then challenged with interference learning, and the effect on memory differed depending on whether reactivation had happened during waking or during slow-wave sleep [4]. In practical terms, a memory reactivated while awake behaved as though it could be disrupted by the competing material, while one reactivated in slow-wave sleep did not show that same vulnerability.
It helps to separate two things that are easy to conflate: how strongly a memory is recalled, and how resistant it is to being overwritten. Interference susceptibility is about the second. A memory can be recalled well in the moment and still be fragile to later competing learning, which is exactly the distinction the wake-versus-sleep contrast brings out [4].
Does it matter which sleep stage the reactivation happens in?
Within sleep, the evidence does not show that slow-wave sleep is a uniquely powerful stage for reactivation. Direct comparisons of cueing during slow-wave sleep versus lighter stage 2 sleep found no significant difference in later memory performance, even though the brain responded differently to cues in the two stages [1][3]. In one study, cues during stage 2 produced stronger oscillatory responses in several frequency bands, yet recall was no better for words cued in either stage, and there was no overall benefit of cued over uncued words at all [1]. The other found larger brain responses to cues in slow-wave sleep and more slow oscillations and spindle complexes there, but none of these measures tracked memory performance [3].
So the wake-versus-sleep difference should not be read as 'deeper sleep is better.' The contrast that matters for interference is between being awake and being asleep, not between one sleep stage and another. The stage-comparison studies speak to how effective reactivation is for strengthening memory, not to how vulnerable a reactivated memory is to competing learning [1][3].
How firm is the interference finding, and what is still unclear?
The direct wake-versus-sleep interference result rests on a single study, so it should be treated as a strong signal rather than a settled rule [4]. Related work on sleep reactivation points to a possible protective role: reactivation during sleep has been discussed as a way of reducing interference and supporting discrimination between similar memories, though that work compared slow-wave sleep with REM sleep rather than with waking [5]. That is consistent with the idea that sleep reactivation shields memories, but it is not the same comparison and does not by itself confirm the waking-versus-sleep contrast.
There is also a caution from the stage-comparison work: reactivation benefits can be less robust than often assumed. One vocabulary study failed to find any overall advantage for cued over uncued words, which the authors took as a reason to question how reliably this effect replicates [1]. That does not overturn the interference finding, but it means the strength of reactivation effects can depend on the task and conditions. The honest summary is that waking reactivation appears to make memories more interference-prone while slow-wave-sleep reactivation appears to protect them, with the caveat that the cleanest evidence for that contrast comes from one experiment [4].
Sources used in this answer
Targeted memory reactivation during slow-wave sleep vs. sleep stage N2: no significant differences in a vocabulary task
Cueing words during stage 2 sleep versus slow-wave sleep produced no difference in later recall, and there was no overall memory benefit of cued over uncued words, despite stronger brain responses to cues in stage 2.
Comparing targeted memory reactivation during slow wave sleep and sleep stage 2
This study compared targeted memory reactivation during slow-wave sleep and stage 2 sleep but did not examine interference susceptibility.
Targeted memory reactivation is not more effective during slow wave sleep than sleep stage 2
Cueing during slow-wave sleep was not more effective for memory than cueing during stage 2 sleep, even though brain responses to cues and slow-oscillation measures differed between stages and none tracked memory performance.
Labile or stable: opposing consequences for memory when reactivated during waking and sleep
Reactivating a memory during waking versus slow-wave sleep had opposing effects on stability, with interference learning affecting the memory differently depending on the state of reactivation.
Does targeted memory reactivation during slow-wave sleep and rapid eye movement sleep have differential effects on mnemonic discrimination and generalization?
Targeted memory reactivation during slow-wave sleep versus REM sleep was examined for mnemonic discrimination and generalization, with reactivation discussed as potentially reducing interference, but waking was not compared.