Dara L. Sosulski - US grants

[unreadable] DESCRIPTION (provided by applicant): A well-functioning olfactory sense is of critical importance, underlying our ability to reject spoiled or contaminated food sources, detect infection and disease, and avoid danger like fire or hazardous chemicals. Our ability to perform these tasks depends on the brain's ability to detect and discriminate relevant odors, but exactly how the brain does this is unclear, and insight into this process is vital for the discovery of better targets for treatment when the olfactory sense fails. In order to investigate how the earliest olfactory regions of the brain encode and process information about innately relevant odors, the following three AIMS are proposed: AIM I: Many compounds isolated from predator or conspecific excretions have been assigned behavioral valences by previous work, but it remains unclear which olfactory subsystem (main or accessory) is important for the detection of these odors. We hypothesize that the olfactory system activated will not correlate with the behavioral valence of the odor (e.g. attractive vs. aversive). We will examine this by testing wild type and TRPC2 knockout mice, which lack a functional vomeronasal/accessory olfactory system, in T-maze and open field assays to determine which olfactory subsystem subserves the behavioral responses to these odors. AIM II: A number of studies have examined how odor information is mapped onto the surface of the OB by the projections of first-order OSNs, which synapse on second-order mitral/tufted (M/T) cells in spheres of neuropil called glomeruli, but few have examined how odors with innate relevance are represented. We hypothesize that innately relevant odors activate a small number of sensitive glomeruli on the lateral surface of the OB. We will test this hypothesis using two-photon laser scanning microscopy (2PLSM) to image glomerular responses in anaesthetized mice that express an indicator of neural activity in all OSNs ("spH mice"), paired with a novel surgical preparation that allows imaging of -50% of the lateral and dorsal OB. AIM III: It has been demonstrated that the representation of neutral odors by OSN projections to the OB varies greatly depending on parameters such as concentration and stimulus context. We hypothesize that the representation of innately relevant odors remains more or less constant across a range of concentrations and contexts, and will test this by imaging glomerular responses with 2PLSM, as per AIM II. [unreadable] [unreadable] [unreadable] [unreadable]