Synaptic function, neuronal development, and detection of life-determining odor cues depend critically on recognition of both aqueous and vapor phase chemical compounds. Derangements in these processes occur in human pathologies with olfactory symptoms including Alzheimer's disease and epilepsy. The sense of smell has extraordinary sensitivity as well as being broadly discriminative - often mutually exclusive capabilities - while exhibiting plastic changes in both peripheral and central circuits. The long-term goals of my lab are to understand how stable odor information is encoded in changing external and internal environments by processes that extend from odorant input to behavioral output. Over the long-term we have focused on four interrelated issues: 1) how odorant structure/olfactory receptor (OR) interactions are represented in neuronal activity; 2) how this activity correlates with odor-guided behavior: 3) how principles of olfactory information processing may be relevant for understanding other brain regions; and 4) how these principles can be used to design artificial devices for recognizing chemicals related to problems ranging from medical diagnosis to the detection of explosives. The present proposal relates to all four goals, but concentrates on the first two. Using a standardized animal model, the tiger salamander, developed in this lab, many anatomical, physiological, molecular, and behavioral data have been obtained. Others and we have used these data to form a defined, testable hypothesis of how odors are encoded by spatially and temporally distributed events in the CNS, but many details still need elucidation. These events appear to form the basis for the broadband, yet highly specific nature of olfactory responses, while accommodating the redundancy and fault tolerance required by an adaptive, plastic system. One of many gaps in understanding this process is characterizing the relationships among many odorant stimuli, numerous ORs, and the distributed nature of the spatio/temporal encoding process. Here we propose to use a combination of molecular, physiological, and behavioral approaches to provide new information on the neuronal basis of odor-guided behavior. Based on our data on the distribution of salamander ORs, we will use a new method of receptor blockade using UV light to examine relationships among odorant structure, epithelial regions of OR expression, and the properties of epithelial and bulbar responses to behaviorally relevant odorants.
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