UBIQUITIN C-TERMINAL HYDROLASE IS AN IMMEDIATE-EARLY GENE ESSENTIAL FOR LONG-TERM FACILITATION IN APLYSIA

The switch from short-term to long-term facilitation of the synapses b etween sensory and motor neurons mediating gill and tail withdrawal re flexes in Aplysia requires CREB-mediated transcription and new protein synthesis. We isolated several downstream genes, one of which encodes a neuron-specific ubiquitin C-terminal hydrolase. This rapidly induce d gene encodes an enzyme that associates with the proteasome and incre ases its proteolytic activity. This regulated proteolysis is essential for long-term facilitation. Inhibiting the expression or function of the hydrolase blocks induction of long-term but not short-term facilit ation. We suggest that the enhanced proteasome activity increases degr adation of substrates that normally inhibit long-term facilitation. Th us, through induction of the hydrolase and the resulting up-regulation of the ubiquitin pathway, learning recruits a regulated form of prote olysis that removes inhibitory constraints on long-term memory storage .