The ability to detect and discriminate between thousands of different odorants begins with olfactory stimuli activating ensembles of receptor neurons that send axonal projections terminating in neuropil regions called glomeruli located on the surface of the olfactory bulb. Mitral/tufted neurons are the primary output neurons of the olfactory bulb, and have primary apical dendrites that extend into the glomerular tufts that are innervated by the olfactory receptor axon terminals. Different odorants activate spatially distinct patterns of glomeruli across the surface of the olfactory bulb. This input organization has been characterized for a wide range of odorants and concentrations. However, mitral/tufted neuron responses are shaped by two layers of inhibitory and excitatory interneurons, a complex arrangement that allows for many possible functions of the bulb. Here, we propose to simultaneously use calcium dyes loaded into sensory axons to examine the input to the bulb, and target the novel fast fluorescent protein voltage sensor ArcLight mitral/tufted neurons to examine the output. These experiments would be the first to simultaneously examine the spatio-temporal patterns of both the input and output of the olfactory bulb.
Current understanding of how different brain regions process sensory information is limited, in part because it has been difficult for current recording techniques to compare the inputs and outputs of a brain structure. The proposed experiments will allow for simultaneous comparison of the input and output of the olfactory bulb. This will allow us to measure the spatio-temporal transfer function of the olfactory bulb, and improve our understanding of olfactory processing, deficits of which have been implicated in several diseases including Alzheimer's.
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