Intermediate-term memory is modulated by the circadian clock.

Sensitization of the tail-siphon withdrawal reflex in Aplysia, a nonassociative form of learning, affords a superb opportunity to investigate the regulation of learning and memory by the circadian clock. The circadian clock has been shown to modulate long-term but not short-term sensitization. However, no previous studies have examined the role of the circadian clock in intermediate-term memory. Noxious stimulation delivered to the side of the animal using a spaced training protocol resulted in canonical intermediate-term sensitization dependent upon both MAPK signaling and protein synthesis. The authors found that intermediate-term sensitization exhibited strong rhythms in expression in both light-dark cycles and constant darkness. Animals trained during the (subjective) day demonstrated significantly more intermediate-term memory than animals trained at night. Baseline responses prior to training were not modulated by the circadian clock. Thus, these results indicate that the circadian clock strongly modulates intermediate as well as long-term memory.