I am interested in the neural basis of stimulus-driven behaviors. I propose a combination of molecular genetic, in vivo imaging and behavioral approaches to understand the neural processing of olfactory information in the mouse brain.
Smell is an essential sense that allows animals to detect food, predators and mates. Olfactory stimuli are recognized by odorant receptors expressed in sensory neurons in the nose. Individual sensory neurons express one of 1300 receptor genes and neurons expressing a given receptor project to a single synaptic structure, called glomerulus, in the olfactory bulb. The patterns of axonal projections are spatially invariant and provide a topographic map of odorant receptor activation in the brain. Information encoded by glomerular activity is transmitted by olfactory bulb projection neurons to several higher olfactory centers in the cortex. Sensory processing at these higher olfactory centers is thought to link odor representations to appropriate behaviors.
Central to understanding olfactory processing is the elucidation of the functional properties of the underlying neural circuits. In an effort to address this fundamental problem in sensory biology, I have altered the patterns of neural activity evoked by odors, by generating transgenic mice in which 95% of all sensory neurons express the same receptor. In vivo imaging and behavioral analyses of these mice suggest a model of olfactory processing in which the recognition of patterns of neural activity, or contrast, is critical for odor detection. To test this model, I will exploit a set of defined genetic perturbations I have created in transgenic mice which alter the expression of odorant receptor genes. I will employ state-of-the-art imaging approaches to reveal how genetically defined patterns of glomerular activity are transformed into higher order odor representations, and I will examine the consequences of such perturbations for innate and learned olfactory-driven behaviors.
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