Entirely synthetic memory inception via dual optogenetic activation of sensory and dopaminergic neurons.

Associative conditioning is a fundamental learning paradigm that links salient stimuli to appropriate behavior. The vinegar fly serves as a key model, forming memories by associating odors with reward or punishment through distinct dopaminergic circuits. A critical question is whether simple co-activation of sensory and neuromodulatory dopaminergic neurons is sufficient for memory formation. We addressed this by optogenetically replacing natural stimuli-odor-evoked activity, punishment, and reward signals-either individually or in combination. Notably, even in a full-substitution paradigm where both olfactory and reinforcement signals were replaced, optogenetic activation successfully implanted synthetic memories. Our findings demonstrate that simple coincident activation of sensory and neuromodulatory neurons is enough to instruct associative memory formation-complex temporal or ensemble activity patterns characteristic of natural stimuli are not required. This work provides a framework for controlling and dissecting memory circuits with all-optical approaches, offering new tools for studying the mechanisms of learning and memory.