Neural circuit mechanisms for multisensory associative learning

Project Summary The brain uses sensory representations to assess risk and predict reward in order to adjust behavior. Per­ ception is a multisensory process. To make reliable predictions, it is advantageous for the brain to combine more than one sensory modality to represent the world. In humans, as in many species, there is evidence for sophisticated forms of learning, such as crossmodal enhancement, where the integration of multiple stimuli from different modalities facilitates memory formation and/or improves discrimination. Because research has primarily focused on studying our senses in isolation, many questions remain with regards to multisen­ sory learning. Are the rules of sensory representation in learning centers similar across sensory modalities? What circuit mechanisms underlie non­linear representations of bimodal cues? How do these affect mul­ tisensory learning? To answer these questions, we must be able to probe and manipulate neural circuits at the site of multisensory integration and learning, which is challenging in many model organisms. Here we propose to leverage a recent synaptic connectivity map of the mushroom body, a well­studied learning center of the fruit fly Drosophila melanogaster, combined with state of the art in vivo imaging and genetic manipulations techniques to accomplish this. The mushroom body has been almost exclusively studied in the context of olfactory learning. However recent connectomics data has revealed that it receives a large fraction of visual inputs. We will determine what kind and how visual information is represented in the princi­ pal cells of the MB (Aim1). We will then extend this characterization to compound visual/olfactory stimuli and characterize circuit mechanisms for nonlinear interactions between these types of information (Aim2). With this knowledge, we will determine stimulus parameters likely to elicit robust multisensory learning and use these in a learning assay under the microscope to probe neural circuitry for multisensory learning (Aim3). This project provide the foundation for a subsequent TargetedBCP R01 aimed at expanding our integrated experimental and theoretical approaches to extract fundamental principles of multisensory learning.