Abstract
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 Alzheimer’s 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.