The encoding of significance during learning: A mechanistic analysis of pattern-sensitive memory formation in Aplysia californica

The benefit to learning of spaced study sessions over continuous study is virtually canonical. However, the mechanisms underlying this spacing effect remain unclear. Here, I begin an exploration of these mechanisms within the model system Aplysia californica. Towards this end, I have identified the simplest training patterns that are permissive for the induction of long-term memory (LTM) in simple behavioral reflexes that permit the mechanisms underlying this induction to be explored at the synaptic and molecular level. Specifically, I have identified a critical training window for the successful pairing of two training trials to result in the acquisition of a LTM for sensitization. Temporally bracketed by unsuccessful (non-permissive for LTM) spacing intervals, the successful spacing interval for 2-trial LTM induction is associated with an equally narrow window of transient MAPK activation within a critical element of the reflex circuitry. I have also demonstrated that blocking MAPK activity during training and for at least 1 hour after training disrupts 2-trial LTM formation.;These data suggest that MAPK activity, a signaling requirement for LTM formation in vertebrates and invertebrates, may provide a molecular mechanism for the establishment of the restricted temporal window observed as a defining feature of 2-trial LTM. Finally, I describe experiments that reveal that a previously established LTM, alter apparent forgetting, nonetheless can alter the patterning requirements for 2-trial LTM induction, so that a non-permissive 2-trial training interval now becomes permissive for LTM formation. In summary, this investigation of the patterning requirements for memory formation in Aplysia has expanded our understanding of learning in this system and identified MAPK as a potential player in establishing the appropriate training interval for LTM formation.