[Research Interests] [Representative Publications] [Lab Members] RESEARCH INTERESTSMolecular and cellular mechanisms underlying the function and development of olfactory sensory neurons. Olfactory sensory neurons of mammals offer rich opportunities to study a range of fundamental questions in the areas of signal transduction, regulation of gene expression, and the development and maintenance of neuronal circuits. Unique features of these cells include the signal transduction in cilial microcompartment, the strictly regulated expression of a large repertoire of odorant receptors, stereotyped patterns of axonal projection, and a dynamically maintained neuronal population. The long-term goal of our research is to capitalize on the unique aspects of olfactory sensory neurons to gain insights into neuronal function and development as well as the sense of smell.
Olfactory sensory neurons, which are located within the olfactory epithelium inside the nose, generate electrical responses to encode odor stimulation. The signal transduction process, which converts the binding of odorous molecules to odorant receptors into the depolarization of the cell membrane, occurs at the cilia extending from the dendrite of olfactory sensory neurons. Over the past two decades, intense studies have elucidated a G protein-coupled, cyclic AMP second messenger-mediated core signal transduction pathway. However, understanding how the olfactory sensory neuron responds to ever changing environmental stimuli requires the knowledge of how the signal transduction pathway is modulated, which allows the sensory neuron to react rapidly to the stimulation, to terminate the response rapidly after the stimulation, and to adjust sensitivity (i.e. to adapt) according to the intensity and duration of odor exposures. We use the ability to manipulate the mouse genome to examine how specific regulatory events targeting specific proteins will influence olfactory signal transduction. Olfactory sensory neurons in the nose form precise connections with neurons in the brain. The olfactory system, olfactory sensory neurons expressing the same odorant receptor, though randomly dispersed in a broad area of the olfactory epithelium, project axons to the same locations in the olfactory bulb of the brain. Further, olfactory sensory neurons have a relatively short life span and are susceptible to damage caused by environmental factors. The neuronal population is continuously renewed throughout life and maintains a conserved connection pattern to the olfactory bulb. We are interested in understanding mechanisms that account for the formation and maintenance of such precise neuronal connections. Our experimental approaches include gene-targeting in mice, molecular and histological characterizations of gene expression, electrophysiological recordings, and behavioral tests. REPRESENTATIVE PUBLICATIONSSong, Y., Cygnar, K.D., Sagdullaev, B., Valley, M., Hirsh, S., Stephan, A., Reisert, J., and Zhao, H. 2008. Ca2+/calmodulin-mediated fast desensitization by the B1b subunit of the CNG channel affects response termination but not sensitivity to recurring stimulation in olfactory sensory neurons. Neuron. (in press). Booker-Dwyer, T., Hirsh, S., and Zhao, H. 2008. A Unique Cell Population in the Mouse Olfactory Bulb Displays Nuclear b-catenin Signaling During Development and Olfactory Sensory Neuron Regeneration. Developmental Neurobiology. (in press). Lane, A.P., Zhao, H., Reed, R.R. 2005. Development of transgenic mouse models for the study of human olfactory dysfunction. Am J Rhinol.19:229-35. Zhao, H., Ivic, L., Otaki, J.M., Hashimoto, M., Mikoshoba, K., and Firestein, S. 1998. Functional expression of a mammalian odorant receptor. Science, 279, 237-242. Lab MembersGraduate Students:
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