Interactions between MAPK and its signaling partners during the formation of long-lasting memory and synaptic facilitation in Aplysia

During the investigation of cellular and molecular mechanisms underlying memory formation, a wide array of molecular elements have been found to be critical. This raises an important question: How do these molecular elements collaborate in the service of memory formation? My dissertation work begins to address this question in Aplysia, a powerful animal model for mechanistic analyses of simple forms of learning and memory. Specifically, we have performed parallel analysis of changes in MAPK and its related molecular partners induced by permissive versus non-permissive patterns of training for long-lasting memory and synaptic facilitation. Importantly, we have examined the interaction between the changes in these individual molecular elements. We found that (i) MAPK activation is differentially regulated by small G-proteins, in response to different patterns of training; (ii) active MAPK is differentially routed to distinct downstream pathways for the expression of distinct forms of memory induced by different patterns of training. These findings suggest that memory formation can be mediated by multiple molecular cascades. Surprisingly, the functional interactions between these molecular elements are highly correlated with the formation of long-lasting plasticity. In response to patterns of training that induce long-lasting memory and synaptic facilitation, (i) MAPK activation is regulated by the balance between interactive ApRas and ApRap activity; and in addition (ii) MAPK activation leads to persistent activation of a kinase that mediates the expression of the memory. Collectively, these findings support the view that the communication between multiple molecular elements is critical for memory formation.