Functional Analysis of Information Processing in the Peripheral Olfactory System - Project summary Sensation leads to perception and guides behavior. Information about the external world is first received by our sensory organs, then preprocessed and reformatted by subcortical structures prior to reaching the cortex where a percept is potentially formed. In olfaction, information reaches the cortex after only two synapses. Despite the critical role of olfaction for animal behavior across phyla, we still have a limited understanding of the principles of information processing in this sensory system. In mammals, inhalation of odors induces broad patterns of spatiotemporal activity across an array of glomeruli in the olfactory bulb, which in turn evoke complex activation patterns in second order neurons, the Mitral and Tufted cells (MTCs). These cells are embedded in a local network of inhibitory neurons and transmit information to higher brain areas. The goal of this proposal is to characterize the transformation of odor responses from glomeruli to MTCs in awake animals, explore the mechanisms underlying this transformation, and reveal its significance for information processing. Our proposal capitalizes on recent technological advances that overcome experimental limitations that have hampered progress in the field. First, we have developed a method for 2-photon calcium imaging of glomeruli and MTCs using fast indicators to record neuronal activity with temporal resolution comparable to electrophysiological recordings. Second, we currently can record responses of both glomeruli and MTCs in the same animal to hundreds of odor stimuli presented over multiple sessions. And third, we have developed a method for identification and characterization of functional connectivity between glomeruli and MTCs, by combining 2-photon imaging of MTCs with optogenetic pattern stimulation of glomeruli. Using this approach, we will characterize the responses of MTCs that are functionally connected to defined glomeruli using a large battery of odor stimuli. This will allow us to analyze the relationship between the response tuning of identified MTCs and the responses of the large glomerular array. Next, we will gain insights into the mechanisms responsible for shaping MTCs responses by optogenetic probing individual connections between glomeruli and MTCs in the presence of odor stimuli. Finally, we will test the idea that the transformation from glomeruli to MTCs plays a role in concentration invariant odor recognition by analyzing both glomeruli and MTC response invariance to changes of odor concentrations. The proposed experiments will generate fundamentally new insights into the rules governing sensory transformations in the peripheral olfactory system and will provide powerful new tools for the study of olfactory function in mammals.
