The role of cAMP response element-binding protein in Drosophila long-term memory.

In Drosophila, the transcription factor cAMP response element-binding protein 2 (dCREB2) has been reported to modulate the formation of long-term olfactory memory (LTM). Overexpression of a repressor isoform of CREB (dCREB2-b) under the control of a heat-shock promoter was reported to block LTM, whereas overexpression of an activator isoform (dCREB2-a) was reported to enhance LTM. A ratiometric model based on these results predicts that the balance of functional dCREB2-a and dCREB2-b provides a switch for memories to remain labile or to become enduring. We show here that the dCREB2-a transgene originally reported to enhance LTM carries a mutation that produces a translational reading-frame shift with the consequent formation of a stop codon at predicted amino acid position 79. Overexpression of this mutant dCREB2-a transgene or a corrected dCREB2-a transgene failed to show any enhancement of LTM. Overexpression of the dCREB2-b repressor transgene, in contrast, produced the anticipated block in LTM formation. We discuss the implications of these findings and propose an alternative model for the role of dCREB in Drosophila LTM.