| Signaling cascades involving mitogen-activated protein kinase (MAPK;ERK1/2), long known to play a role in developmental processes such as cellular proliferation and differentiation, are also important for processes underlying memory formation. The marine mollusk Aplysia californica is a useful system for studying the molecular and cellular mechanisms of learning and memory for sensitization in a simple reflex. Although it is known that MAPK activity is required for long-term facilitation and memory for sensitization, its specific role across various forms of long-term plasticity is largely unknown. The aim of this thesis project was to examine the possible role of MAPK in these various forms of memory in this model system.; We have examined the role of MAPK in two distinct forms of long-lasting memory: Activity-dependent intermediate-term memory (AD-ITM) and long-term memory (LTM) for sensitization. Our results indicate that increased MAPK activity in the tail sensory neurons (SNs) induced by behavioral training regulates the induction of AD-ITM and the consolidation of LTM. Furthermore, we reveal that these temporally and mechanistically distinct forms of memory recruit different MAPK signaling cascades. The induction of AD-ITM activates MAPK, which in turn causes protein kinase C (PKC) to translocate to the plasma membrane and thereby regulate the activity of preexisting effectors. In contrast, during the consolidation of LTM, persistently activated MAPK translocates to the nucleus to upregulate effector genes necessary for long-term changes in synaptic strength.; In sum, these results provide the first evidence that within an identified neuronal population, MAPK functions as a molecular node that interprets pattern-sensitive cues by directing the activation of behaviorally specific downstream molecular cascades. |
