Multisensory learning binds modality-specific neurons into a cross-modal memory engram

Associating multiple sensory cues with objects and experience is a fundamental brain process that improves object recognition and memory performance. However, neural mechanisms that bind sensory features during learning and augment memory expression are unknown. Here we demonstrate multisensory appetitive and aversive memory in Drosophila. Combining colors and odors improved memory performance, even when each sensory modality was tested alone. Temporal control of neuronal function revealed visually-selective mushroom body Kenyon Cells (KCs) to be required for both enhancement of visual and olfactory memory after multisensory training. Voltage imaging in head-fixed flies showed that multisensory learning binds activity between streams of modality-specific KCs, so that unimodal sensory input generates a multimodal neuronal response. Binding occurs between regions of the olfactory and visual KC axons, which receive valence-relevant dopaminergic reinforcement, and is propagated downstream. Dopamine locally releases GABA-ergic inhibition to permit specific microcircuits within KC-spanning serotonergic neurons to function as an excitatory bridge between the previously modality-selective KC streams. Cross-modal binding thereby expands the olfactory memory engram by recruiting visual path KCs to become odor responsive. This broadening of the engram improves memory performance after multisensory learning and permits a single sensory feature to retrieve the memory of the multimodal experience.