CREB1 ENCODES A NUCLEAR ACTIVATOR, A REPRESSOR, AND A CYTOPLASMIC MODULATOR THAT FORM A REGULATORY UNIT CRITICAL FOR LONG-TERM FACILITATION

Although CREB seems to be important for memory formation, it is not kn own which of the isoforms of CREB, CREM, or ATF1 are expressed in the neurons that undergo long-term synaptic changes and what roles they ha ve in memory formation. We have found a single Aplysia CREB1 gene homo logous to both mammalian CREB and CREM and have characterized in the s ensory neurons that mediate gill-withdrawal reflex the expression and function of the three proteins that it encodes: CREB1a, CREB1b, and CR EB1c. CREB1a is a transcriptional activator that is both necessary and , upon phosphorylation, sufficient for longterm facilitation. CREB1b i s a repressor of long-term facilitation. Cytoplasmic CREB1c modulates both the short- and long-term facilitation. Thus, in the sensory neuro ns, CREB1 encodes a critical regulatory unit converting short- to long -term synaptic changes.