Mammals have the remarkable power of detecting and discriminating thousands of odors. This largely relies on the various types of olfactory receptors expressed in the primary sensory neurons in the nose. Olfactory information is likely encoded by combinations of different receptors (neurons); i.e., a single receptor can respond to multiple odorants and a single odorant can be recognized by multiple receptors. However, very limited knowledge is available on how broadly or narrowly these receptors are tuned and on how these receptors are combined to encode odor mixtures. The rodent main olfactory system contains millions of sensory neurons expressing >1000 receptors and presents serious challenges for addressing these questions. Recently, we discovered that the mouse septal organ, a small patch of olfactory epithelium located in the ventral base of the nasal septum, mainly expresses a few defined receptors. Nearly 50% of the septal organ cells express the MOR256-3 receptor and approximately 43% express seven other receptors at varying levels. Furthermore, a single cell expresses only one receptor. The septal organ offers a unique opportunity to study how individual sensory neurons respond to single or mixed odorants in relation with the receptors they express and the central targets they innervate under physiological conditions. We will provide a relatively complete analysis of this kind by combining physiological, molecular, and histological approaches, and test specifically the following hypotheses. First, different olfactory receptors play different roles in odor detection and discrimination. Some olfactory receptors, exemplified by the major septal receptors, are much more broadly tuned than others and serve as general odor detectors in the nose. Second, different olfactory receptors behave differently in sensing odor mixtures. The broadly-tuned receptors tend to become less active when stimulated by a mixture and the narrowly-tuned receptors remain active as long as their preferred ligands are present. Third, different olfactory receptors (broadly vs narrowly-tuned) have different central projection patterns to the olfactory cortex. Overall, implementing such a project will greatly enhance our knowledge about olfactory coding and processing in general and shed light on the behavioral significance of the septal organ.
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