Ngo, H.-V. | bioRxiv Science

bioRxiv2025

Sleep to remember, sleep to protect: increased sleep spindle and theta activity predict fewer intrusive memories after analogue trauma

Recent evidence shows a strong correlative link between sleep disturbances and intrusive memories after traumatic events, presumably due to insufficient (nocturnal) memory integration. However, the underlying mechanisms of this link and the role of specific neural activities during sleep are poorly understood so far. Here, we investigated how the intra-individual affective response to an experimental trauma predicts changes in oscillatory activity during subsequent sleep and how these changes predict the processing of the experimental trauma. In a randomized within-subject comparison, twenty-two female, healthy participants (23.14 {+/-} 2.46 years) watched a well-validated film clip including "traumatic" contents and a neutral film clip before bedtime on two separate nights. Heart rate was recorded during the film clips and nocturnal brain activity was recorded using 64-channel high-density EEG during subsequent nights. Intrusive memories were assessed via a seven-days diary and negative affect was assessed using laboratory trauma film reminders one week after the trauma film. An increased intra-individual heart rate during the trauma film predicted higher intra-individual sleep spindle amplitude the following night. Increased theta activity (4.25 - 8 Hz) during rapid eye movement (REM) sleep after the trauma film predicted fewer trauma film related intrusive memories and negative affect. Likewise, an increase in sleep spindles after the trauma film predicted fewer trauma film related intrusive memories. Our findings suggest that an experience-dependent up-regulation of these nocturnal oscillatory activity patterns, which are known to be involved in adaptive memory consolidation processes, serves as a protective factor against trauma-related intrusive memory development. Particularly, increased theta activity during REM sleep and sleep spindle activity seem to be of importance here.

neuroscience↗

bioRxiv2019

The gap junction blocker mefloquine impairs sleep-dependent declarative memory consolidation in humans

During sleep, the time-compressed replay of engrams acquired during preceding wakefulness drives memory consolidation. We demonstrate in healthy humans that direct electrical coupling between neurons via gap junctions, i.e., electrical synapses, contributes to this beneficial effect of sleep. Twenty male participants learned a declarative word-pair task and a procedural finger sequence tapping task before receiving the antimalarial mefloquine that is known to block electrical synapses. Retrieval was tested after a retention interval of approximately 20.5 hours that included nocturnal sleep. As predicted, mefloquine given before sleep impaired the retention of declarative memory. In contrast, this effect was absent in control groups, which stayed awake or received mefloquine after sleep. Irrespective of sleep or administration time, mefloquine enhanced retention performance on the procedural memory control task. We conclude that sleep-dependent processes relying on electrical neuronal coupling enable hippocampus-dependent declarative memory consolidation, presumably via time-compressed hippocampal replay of memory traces within sharp-wave/ripple complexes. The recruitment of this understudied form of neuronal information transfer may be necessary to achieve fast-paced memory reprocessing during sleep. Considering that drugs targeting neurochemical synapses have recently fallen short of substantially advancing the treatment of memory impairments in Alzheimers disease, schizophrenia or during normal aging, unraveling the contribution of gap junctions to sleep-dependent declarative memory formation can be expected to open new therapeutic avenues. Significance statementSleep supports the strengthening and transformation of memory content via the active replay of previously encoded engrams. Surprisingly, blocking neurochemical synaptic transmission does not impair this function of sleep. Here we demonstrate that the direct electrical coupling between neurons via electrical synapses (gap junctions) is essential for the sleep-dependent formation of declarative memory, i.e., memory for episodes and facts. These findings are in line with the assumption that electrical synapses enable time-compressed neuronal firing patterns that emerge during sleep and drive declarative memory consolidation. Electrical synapses have so far not been linked to higher-order brain functions in humans; their contribution to sleep-dependent memory processing may provide a novel target for sleep-related clinical interventions.

neuroscience↗