Bulbar maps to retronasal smell by optical calcium imaging and fMRI in acute rat

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DESCRIPTION (provided by applicant): The flavor of a food is comprised of information from multiple sensory modalities. One major modality is the sense of smell. During food ingestion it is the retronasal smell, not the orthonasal route that informs about the chemical make-up of food. Functional imaging studies in humans have provided important insights into the neural bases of multimodal flavor integration, and provided support for the hypothesis that brain processing of ortho- and retronasal smell differs. Yet, the upstream olfactory bulbs of humans are not accessible to fMRI. Limited evidence suggests that the neural representations of odorants at the first stage of processing olfactory information, the olfactory bulb (OB), differ between these two modes of smell. However, to date no study has directly investigated odor maps to retronasal smell. Virtually every study on bulbar maps in vertebrates is on orthonasal smell only. In addition to the retronasal maps remaining unknown, it also remains unclear how representations are transformed across the first olfactory synapse in the glomerulus. To date no study has unambiguously compared presynaptic and postsynaptic responses in OB. More generally, it remains unclear how optically imaged neural calcium responses relate to those reported by peri/post-synaptic fMRI BOLD. To fill in these gaps in our knowledge of flavor encoding and transformation in the OB and its translation to human fMRI studies, we propose to image retronasal and orthonasal odor maps in the anesthetized rat. We propose two comparative sets of studies. In the first Aim, we will image only the dorsal OB at glomerular resolution to only orthonasal responses by using innovative micro-fMRI with phased coil arrays and by using presynaptic calcium dyes, to investigate their neurobiological relation, in the same animal. In the second Aim we will image responses to both orthonasal and retronasal odors across the entire OB with fMRI, and the dorsal OB optical calcium imaging, in the same animal. Whereas fMRI has access to the entire OB, optical imaging of the dorsal OB has a higher spatial and temporal resolution. For both complementary approaches the methods will be essentially the same, uniquely allowing us to compare the odor maps derived by both techniques. To further understand the effects of parameters relevant to olfaction, we will image responses to an array of stimuli with a large span of lipophilicity. We will furthermore investigate the effects of odor flow rate and odor concentration on the odor maps of the OB. Together these studies are intended to provide fundamentally new knowledge about the neural mechanisms of retronasal smell, and of bulbar neural transformations using a rat model and these studies are a first step toward translation of rodent functional imaging to human olfactory fMRI research. PUBLIC HEALTH RELEVANCE: This project investigates the neural encoding of retronasal smell. Retronasal smell forms an obligatory and important aspect of the flavor of food. Because flavor plays a central role in motivating food intake, research on the neural mechanisms of flavor perception is essential for understanding the sensory factors that contribute to eating-related disorders such as obesity, diabetes and cardiovascular disease.