The Role of cAMP Response Element-Binding Protein inDrosophilaLong-Term Memory

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Abstract
InDrosophila,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 inDrosophilaLTM.