Inducible repression of CREB function disrupts amygdala-dependent memory.

Evidence from Aplysia, Drosophila, mice, and rats indicates that the CREB (cAMP/Ca2+ responsive element binding protein) family of transcription factors is critical for long-term memory. Recent findings, however, suggest that performance abnormalities may contribute to the memory deficits attributed to CREB manipulations in mammals. To clarify the role of CREB in memory, we used a paradigm, conditioned taste avoidance, that places few performance demands on the subject. We show that lesioning or blocking protein synthesis in the basolateral amygdala of mice disrupts conditioned taste aversion. Furthermore, either chronically or acutely disrupting CREB function in two different types of genetically modified mice blocks memory for conditioned taste aversion measured 24 h following training. Together, these findings indicate that CREB-mediated transcription and protein synthesis are required for conditioned taste aversion memory.