Transient mitogen-activated protein kinase activation is confined to a narrow temporal window required for the induction of two-trial long-term memory in Aplysia

Although it is commonly appreciated that spaced training is superior to massed training in memory formation, the molecular mechanisms underlying this feature of memory are largely unknown. We previously described the selective benefit of multiple spaced (vs massed) training trials in the induction of long-term memory (LTM) for sensitization in Aplysia californica. We now report that LTM can be induced with only two spaced training trials [tail shocks (TSs)] when the second TS is administered 45 min after the first. In contrast, spacing intervals of 15 and 60 min are ineffective. This surprisingly narrow permissive training window for two-trial LTM is accompanied by an equally narrow window of transient mitogen-activated protein kinase (MAPK) activation, a necessary signaling molecule for LTM induction, at 45 min after a single TS. Thus, the transient recruitment of MAPK following a single TS may provide a narrow molecular window for two-trial LTM formation.