Mechanisms of inhibitory processing in the olfactory bulb and its contribution to olfactory discrimination behavior

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Inhibitory circuits emerge as a key mechanism in early olfactory processing and odor discrimination behavior in mice. Our recent work has established a direct link between inhibitory interactions of granule cells and mitral/tufted cells in the olfactory bulb and odor discrimination behavior. After establishing that inhibition defines physiologically relevant behavioral features, a focus of this grant is the elucidation of the mechanistic nature of olfactory bulb inhibitory circuits: How does inhibition shape odor representations? This will be addressed by spatio-temporally targeted molecular perturbations, behavioral testing, in vivo analysis of odor-evoked responses and novel optogenetic tools. Firstly, glutamatergic synaptic transmission between granule cells and mitral/tufted cells will be blocked by specifically deleting all ionotropic glutamate receptor subunits but GluA2 in granule cells. The consequences of this perturbation will be assessed on the cellular, in vivo network and behavioral levels. Taking advantage of our previous efforts, the latter will be carried out in an entirely automated approach, ensuring minimal variability and acquisition of a larger number of behavioral parameters. Then, odor-evoked responses in mitral/tufted cells will be observed before and after altering phasic inhibition. Dosed pharmacological as well as optogenetic silencing of interneuron populations including granule cells and periglomerular cells will be employed to gauge the distinct contribution of different sets of interneurons to inhibitory processing. Finally, these data will be incorporated into our existing mathematical model of olfactory bulb function.