Ubiquitin-mediated proteolysis in learning and memory.

Sensitization of defensive reflexes in Aplysia is a simple behavioral paradigm for studying both short- and long-term memory. In the marine mollusk, as in other animals, memory has at least two phases: a short-term phase lasting minutes and a long-term phase lasting several days or longer. Short-term memory is produced by covalent modification of pre-existing proteins. In contrast, long-term memory needs gene induction, synthesis of new protein, and the growth of new synapses. The switch from short-term (STF) to long-term 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 subunits, which is essential for initiating long-term stable memory, occurs through the ubiquitin-proteasome pathway.