Olfactory neuromodulation of visual circuits and behavior

Project summary A significant percentage of people in the US suffer from disabilities resulting from traumatic injury, stroke, or degenerative disease which result in enigmatic deficits in cognitive function. Therefore, an understanding of the fundamental properties of neuronal circuits for complex brain function, and how these circuits are modulated by biogenic amines, will sharpen our understanding of the normal brain, thereby highlighting pathology and facilitating treatments. A major function of the brain is to integrate information across sensory modalities to enable sharp and robust perception. The cell-circuit mechanism for how different sensory modalities interact is not well understood. This project will capitalize on the significant experimental advantages of the fruit fly Drosophila to explore the molecular logic and neural connections that produce an elementary form of multisensory integration perception. The fly displays robust multisensory perception, integrating olfactory signals with visual processing to enhance perceptual abilities. Furthermore, sensory circuits have been shown to be under robust neuromodulatory control by biogenic amines. Similar processes have been localized to sub- cortical and cortical pathways in humans and non-human primates. The fly has a numerically compact nervous system, with which highly advanced genetic techniques can be used to identify, manipulate, and record activity from individual neurons and neurosecretory cells, as well as their upstream and downstream synaptic partners and molecular components. The PI hypothesizes that the fly brain couples olfactory sensory detection to visual processing through neuromodulatory cells that carry the chemical equivalent of norepinephrine. The PI will perform two-photon Ca2+ imaging to ‘read’ activity from live flies in response to stimuli the PI has discovered elicit robust multi-modal integration behavior within a virtual reality system. The PI will use optogenetics imaging to ‘write’ signals into these circuit pathways to assess input-output functions from an intact behaving fly.