EXCEED THE SPACE PROVIDED. This application is for renewal of research directed toward understanding the detection, discrimination, and transduction of sensory information by neurons of the vomeronasal organ (VNO). There has been significant advancement on the principles of signal transduction and odor detection/discrimination by olfactory receptor neurons (ORNs) in the main olfactory epithelium (MOE), but surprisingly little is known about the functional properties of sensory neurons in the VNO. The main goal of this project is to overcome this critical gap between MOE and VNO studies by investigating response properties of mouse vomeronasal neurons (VNs) and examine the cellular and molecular mechanisms that mediate chemosensory detection in these cells. To reach this goal, experiments in this application will take advantage of newly developed mouse VNO preparations by which the functional analysis of pheromone-induced activity in VNs using electrophysiological and high resolution optical imaging techniques can be integrated with the analysis of the pharmacological and molecular properties of these cells. As a result, it is now possible to define the stimulus range, also known as 'receptive field', that can be detected by the mouse VNO and to conduct functional mapping studies that are designed to reveal the basic organization of pheromone detection in this tissue. Other experiments will determine the mechanisms that underlie the detection of chemical signals in VNs and dissect the steps mediating pheromone transduction in these neurons. Taken together, this research will significantly advance our understanding of the mechanisms that underlie pheromone recognition and discrimination at the first stage of the mouse accessory olfactory system and fill critical gaps in our current knowledge. These experiments are not only fundamentally important to pheromone coding and the organization of the sense of smell, but also to understanding principles of chemical communication regulating sexual, hormonal, and reproductive function in mammals.
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| Leinders-Zufall, Trese; Cockerham, Renee E; Michalakis, Stylianos et al. (2007) Contribution of the receptor guanylyl cyclase GC-D to chemosensory function in the olfactory epithelium. Proc Natl Acad Sci U S A 104:14507-12 |
| Kelliher, Kevin R; Ziesmann, Jurgen; Munger, Steven D et al. (2003) Importance of the CNGA4 channel gene for odor discrimination and adaptation in behaving mice. Proc Natl Acad Sci U S A 100:4299-304 |
| Leypold, Bradley G; Yu, C Ron; Leinders-Zufall, Trese et al. (2002) Altered sexual and social behaviors in trp2 mutant mice. Proc Natl Acad Sci U S A 99:6376-81 |
