Both long-term behavioral memory and synaptic plasticity require protein synthesis, some of which may occur locally at specific synapses. Cytoplasmic polyadenylation element–binding (CPEB) proteins are thought to contribute to the local protein synthesis that underlies long-term changes in synaptic efficacy, but a role has not been established for them in the formation of long-term behavioral memory. We found that the Drosophila melanogaster CPEB protein Orb2 is acutely required for long-term conditioning of male courtship behavior. Deletion of the N-terminal glutamine-rich region of Orb2 resulted in flies that were impaired in their ability to form long-term, but not short-term, memory. Memory was restored by expressing Orb2 selectively in fruitless (fru)-positive γ neurons of the mushroom bodies and by providing Orb2 function in mushroom bodies only during and shortly after training. Our data thus demonstrate that a CPEB protein is important in long-term memory and map the molecular, spatial and temporal requirements for its function in memory formation.
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We thank M. Novatchkova for bioinformatic analysis of CPEB proteins, R. Fuchs and E. Viragh for technical assistance, R. Davis for the TARGET stocks, K. Golic and E. Demir for stocks and vectors for homologous recombination, F. Bertolucci for advice on learning assays, R. Neumüller for help in examining mushroom body morphology, and M. Heisenberg, A. Keene and S. Rumpel for comments on the manuscript. We also thank M. Heisenberg for generously hosting K.K. during the initial behavioral assays and for his constant support and advice. This work was supported by funding from Boehringer Ingelheim and the Austrian Academy of Sciences.
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Keleman, K., Krüttner, S., Alenius, M. et al. Function of the Drosophila CPEB protein Orb2 in long-term courtship memory. Nat Neurosci 10, 1587–1593 (2007). https://doi.org/10.1038/nn1996
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