The role of tyrosine kinase signaling cascades in different forms of neuronal plasticity in Aplysia californica.

摘要

Tyrosine kinases, long known to play a role in developmental processes such as cellular proliferation and differentiation, have recently also been implicated in processes underlying memory formation. The marine mollusk Aplysia californica has proven to be a useful system for studying cellular mechanisms of learning and memory for sensitization in a simple reflex. Although several molecular steps have been elucidated in the acquisition of this reflex memory, the role of tyrosine kinase signaling cascades is virtually unexplored. The aim of this thesis project was to examine the possible role of tyrosine kinases in various forms of neuronal plasticity and memory in this model system.; I examined two different forms of short-term plasticity (excitability and short-term synaptic facilitation (STF)) and a form of long-term plasticity (long-term synaptic facilitation (LTF)). My results indicate that tyrosine kinases modulate excitability of tail sensory neurons but are not required for the induction of STF by the neuromodulator serotonin (5HT). In addition to its role in excitability, tyrosine kinase activity is required for LTF at sensory-motor synapses induced by a repeated presentation of 5HT. Moreover, experimentally induced increases in endogenous tyrosine kinase activity enhances the induction of LTF by converting a single pulse of 5HT, which normally only induces STF, to a stimulus sufficient for the induction of LTF. This finding suggests that tyrosine kinase activity may play a role in processes contributing to consolidation of short-term memory to long-term memory. My results further show that activation of tyrosine kinases recruits mitogen-activated protein kinase activity as well as transcriptional and translational processes. Finally, I found that increases in endogenous tyrosine kinase activity not only enhance the induction of LTF, but also enhance the induction of long-term memory for sensitization.; These results provide the first evidence of a role for tyrosine kinase signaling in different forms of plasticity in Aplysia , and elucidate the molecular mechanism by which LTF is induced and linked it to memory in the behaving animal.