Dopamine-gated memory selection during slow wave sleep

Abstract

The human brain selectively stores knowledge of the world to optimise future behaviour, automatically rehearsing, contextualising or discarding information to create a robust record of experiences. Storage or forgetting evolves over time, particularly during sleep. We sought to test how dopamine shaped long term memory formation before and during sleep. We administered dopamine (L-DOPA tablet) during learning, re-learning, consolidation or retrieval of word lists in two independent double-blind randomised placebo-controlled cross-over studies of healthy older adults (study 1 n = 35, study 2 n = 32). During consolidation, nocturnal dopamine accelerated forgetting for words presented once, but did not affect words presented twice from forgetting. Overnight dopamine increased total slow wave sleep duration by approximately 11%. The effect of dopamine on memory correlated with increased spindle amplitude, which was maximised near slow oscillation peaks, suggesting dopamine-dependent memory processing modulates spindles dependent on slow-oscillation phase. Pharmaceutical modification of slow wave sleep holds great promise for improving old age – potential benefits could include cognitive enhancement and Alzheimer’s prevention.