Abstract
How information is integrated across different forms of learning is crucial to understanding higher cognitive functions. Animals form classic or operant associations between cues and their outcomes. It is believed that a prerequisite for operant conditioning is the formation of a classical association. Thus, both memories coexist and are additive. However, the two memories can result in opposing behavioral responses, which can be disadvantageous. We show that Drosophila classical and operant olfactory conditioning rely on distinct neuronal pathways leading to different behavioral responses. Plasticity in both pathways cannot be formed simultaneously. If plasticity occurs at both pathways, interference between them occurs and learning is disrupted. Activity of the navigation center is required to prevent plasticity in the classical pathway and enable it in the operant pathway. These findings fundamentally challenge hierarchical views of operant and classical learning and show that active processes prevent coexistence of the two memories.