Environmental stimuli are recognized by sensory neurons and this information is transmitted to the brain where it is decoded to provide an internal representation of the external world. Vertebrates can recognize and discriminate a large number of odorants of diverse molecular structure. Humans, for example, are capable of distinguishing among thousands of distinct odors. Although odorants often exhibits widely different structures, subtle changes in molecular structure can lead to striking differences in perceived odor. How does the vertebrate olfactory system recognize and discriminate the vast array of molecules which we define as odorant? The mechanisms underlying olfactory discrimination are likely to involve the combinatorial integration of sensory inputs. The determinants of these combinatorials may exist at several levels. First, the ligand specificities of the odorant receptors will determine the number of receptors which are used to recognize and identify a specific ligand as a unique odor. Second, the number of receptors expressed per olfactory neurons will dictate the complexity required to identify activity from a single type of receptor. If each sensory neuron expresses a single odorant receptor gene, then the brain could identify the activation of a given receptor express small overlapping subsets of receptors, such that the activation of a single receptor would be identified only through a more complex comparison of activities among different neurons. Third, spatially defined inputs at the olfactory bulb may be used to identify activity from different olfactory neurons. The degree or extent of convergence will determine the complexity necessary to identify the activity from a single class of olfactory neurons. Finally, the topographic patterns of the projections in the olfactory bulb are likely to be reflected in some way in the projections to the olfactory cortex. Elucidation of the logic used of decode olfactory information therefore requires a determination of (i) the number of different odorant receptors employed by the olfactory system, (ii) the odorant specificities of individual receptors, (iii) the pattern of odorant receptor expression in olfactory neurons, and (iv) the topography of projections of specific olfactory neurons in the olfactory bulb. In this application, we propose experiments to address these issues directly using cloned odorant receptor probes from the simple olfactory system of the channel catfish. The results from our proposed investigations will allow an eventual understanding of the cellular and molecular mechanisms underlying olfactory discrimination.
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