Ubiquitin-mediated proteolysis in learning and memory

Sensitization of defensive reflexes in Aplysia is a simple behavioral parad igm for studying both short- and long-term memory. In the marine mollusk, a s in other animals, memory has at least two phases: a short-term phase last ing minutes and a long-term phase lasting several days or longer Short-term memory is produced by covalent modification of pre-existing proteins. In c ontrast, long-term memory needs gene induction, synthesis of new protein, a nd the growth of new synapses. The switch from short-term (STF) to long-ter m facilitation (LTF) in Aplysia sensory neurons requires not only positive regulation through gene induction, but also the specific removal of several inhibitory proteins. One important inhibitory protein is the regulatory (R ) subunit of the cAMP-dependent protein kinase (PKA). Degradation of R subu nits, which is essential for initiating long-term stable memory, occurs thr ough the ubiquitin-proteasome pathway.