ABSTRACT (Parent Grant) How taste and odor stimuli become integrated and how retronasal odorants are processed are two fundamental questions in flavor neuroscience. Functional imaging studies in humans have provided important insights into the neural bases of multimodal flavor integration, yet cannot address issues requiring higher spatio-temporal resolution or experimental manipulation of neural activity or of experience, nor evaluate the human olfactory bulb (OB). To address these limitations, the goal of the present project is to establish the transgenic mouse as a novel flavor model and to investigate the neural mechanisms of flavor integration and retronasal smell. We have now established that retronasal olfaction occurs in mice and rats as it does in humans. A first study will employ optical calcium imaging to measure spatio-temporal patterns evoked in the olfactory bulb associated with the oral ingestion of odorants by awake head-fixed transgenic GCaMP mice performing an odor detection task. We will also explore the neuro-behavioral repertoire of free-moving mice carrying a mobile head-mounted miniature imaging microscope. The effects of odor properties, active sampling (sniffing), ingestion (swallowing), hunger and flavor-experience dependent odor-taste integration on retronasal OB responses will be assessed during food exploration, approach and ingestion. We have now established that the temporal dynamics of the OB, i.e. the relative onset delays among glomeruli, are detectable by mice down to 15 ms. To determine whether retronasal temporal information in the OB, which differs fundamentally between ortho- and retronasal smell, contributes to downstream processes, we will ask what the temporal discrimination thresholds are for optogenetically modified mice during various phases of the sniff-cycle. We will next ask whether the dynamics of retronasal OB activity played back onto the OB is discriminable. Last, we will ask if different glomerular onset sequences are discriminable. Importantly, we will assess how these three measures depend on sniff-phase. Together these studies are intended to provide fundamentally new knowledge about the neural mechanisms of flavor perception using the experimentally powerful transgenic mouse models.