An opposing self-reinforced odor pre-exposure memory produces latent inhibition in Drosophila

Prior experience of a stimulus can inhibit subsequent acquisition or expression of a learned association of that stimulus. However, the neuronal manifestations of this learning effect, named latent inhibition (LI), are poorly understood. Here we show that odor pre-exposure produces LI of appetitive olfactory memory performance in Drosophila. Behavioral expression of LI requires that the context during memory testing resembles that during the odor pre-exposures. Odor pre-exposure forms an aversive memory that requires dopaminergic neurons that innervate the {gamma}2'1 and 3 mushroom body compartments - those to 3 exhibit increasing odor-driven activity with successive pre-exposures. In contrast, odor-specific responses of the corresponding mushroom body output neurons are suppressed. Odor pre-exposure therefore recruits specific dopaminergic neurons that provide teaching signals that attach negative valence to the odor itself. LI of Drosophila appetitive memory consequently results from a temporary and context-dependent retrieval deficit imposed by competition with this short-lived aversive memory.