Wakefulness regulation of memory encoding and retrieval: structure and activity

Sleep-wake states are fundamental regulators of memory processing. While memory consolidation relies on sleep, memory encoding and retrieval depend primarily on wakefulness. Although the role of sleep in memory consolidation has been extensively characterized, the contribution of wakefulness to memory encoding and retrieval remains less systematically summarized. In this review, we synthesize current evidence on how wakefulness regulates memory through two key dimensions: (i) structural organization, defined by the anatomical innervation of memory-related brain regions by the wakefulness system; and (ii) activity-dependent regulation, in which arousal states modulate the efficiency of memory encoding and retrieval. We highlight three major mechanisms-memory engrams, synaptic plasticity and neural oscillations-and propose adult hippocampal neurogenesis (AHN) as an additional timescale-specific mechanism linking wakefulness to memory. Finally, we discuss how wakefulness abnormalities disrupt memory encoding and retrieval in aging, Alzheimer's disease and post-general anesthesia, and suggest that moderate enhancement of arousal level provides a novel strategy for improving memory function.