@article {Zhao2021.01.13.426486, author = {Bohan Zhao and Jiameng Sun and Qian Li and Yi Zhong}, title = {Differential Conditioning Produces Merged Long-term Memory in Drosophila}, elocation-id = {2021.01.13.426486}, year = {2021}, doi = {10.1101/2021.01.13.426486}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Multiple spaced trials of aversive differential conditioning can produce two independent longterm memories (LTMs) of opposite valence. One is an aversive memory for avoiding the conditioned stimulus (CS+), and the other is a safety memory for approaching the non-conditioned stimulus (CS-). Here, we show that a single trial of aversive differential conditioning yields one merged LTM (mLTM) for avoiding both CS+ and CS-. Such mLTM can be detected after sequential exposures to the shock-paired CS+ and unpaired CS-, and be retrieved by either CS+ or CS-. The formation of mLTM relies on triggering aversive-reinforcing dopaminergic neurons and subsequent new protein synthesis. Expressing mLTM involves αβ Kenyon cells and corresponding approach-directing mushroom body output neurons (MBONs), in which similar-amplitude long-term depression of responses to CS+ and CS- seems to signal the mLTM. Our results suggest that animals can develop distinct strategies for occasional and repeated threatening experiences.Competing Interest StatementThe authors have declared no competing interest.}, URL = {https://www.biorxiv.org/content/early/2021/01/31/2021.01.13.426486}, eprint = {https://www.biorxiv.org/content/early/2021/01/31/2021.01.13.426486.full.pdf}, journal = {bioRxiv} }