The last several years have witnessed a molecular revolution in the olfactory system. The turning point in this revolution was the seminal discovery, now seven years ago, of a large multigene family in mammals that encodes odor receptors. However, the molecular biology of odor receptors has not been fully integrated with the anatomy and the physiology of the olfactory system. We are aware that the expectations raised by the isolation of odor receptor genes have yet to be fully realized. We have concluded that it is imperative that we begin now to explore the relations between the molecular specificity at the level of the olfactory sensory neuron, the specificity of anatomical organization among the glomeruli in the olfactory bulb and finally, the parameters that may influence the intracellular distribution and dynamics of odor receptor proteins. The present application seeks support for an innovative collaborative program in which all of the investigator share common aims and reagents. Each project brings to the program a unique expertise that enables us to test, from multi-disciplinary perspectives, specific hypotheses regarding the molecular mechanisms of odor coding and mapping. A common theme is the use of genetically engineered mice. Project 1 addresses functional specificity of odor receptors by using and constructing gene-targeted strains of mice. Project 2 uses gene-targeted mice to assess the specificity of synaptic circuits in the olfactory bulb, and gene transfer approaches to identify the parameters that may influence odor receptor protein targeting within the sensory neuron. Project 3 uses adenoviral vectors and gene-targeted mice to characterize the determinants of odorous ligand binding to specific odor receptors. Targeted mutagenesis in the mouse, molecular biology, calcium imaging, advanced anatomical techniques, and novel brain imaging methods are merged in this consortium of laboratories with different backgrounds and expertise. Collectively, we anticipate that this focused and multi- disciplinary set of projects will lead to significant advances in understanding the mechanisms of odor coding and mapping.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Program Projects (P01)
Project #
5P01DC003887-04
Application #
6516199
Study Section
Communication Disorders Review Committee (CDRC)
Program Officer
Davis, Barry
Project Start
1999-07-01
Project End
2004-06-30
Budget Start
2002-07-01
Budget End
2004-06-30
Support Year
4
Fiscal Year
2002
Total Cost
$1,010,412
Indirect Cost
Name
Yale University
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Treloar, Helen B; Uboha, Ulyana; Jeromin, Andreas et al. (2005) Expression of the neuronal calcium sensor protein NCS-1 in the developing mouse olfactory pathway. J Comp Neurol 482:201-16
Treloar, Helen B; Gabeau, Darlene; Yoshihara, Yoshihiro et al. (2003) Inverse expression of olfactory cell adhesion molecule in a subset of olfactory axons and a subset of mitral/tufted cells in the developing rat main olfactory bulb. J Comp Neurol 458:389-403
Lipscomb, Brian W; Treloar, Helen B; Klenoff, Jason et al. (2003) Cell surface carbohydrates and glomerular targeting of olfactory sensory neuron axons in the mouse. J Comp Neurol 467:22-31
Ma, Minghong; Grosmaitre, Xavier; Iwema, Carrie L et al. (2003) Olfactory signal transduction in the mouse septal organ. J Neurosci 23:317-24
Treloar, Helen B; Feinstein, Paul; Mombaerts, Peter et al. (2002) Specificity of glomerular targeting by olfactory sensory axons. J Neurosci 22:2469-77
Lipscomb, Brian W; Treloar, Helen B; Greer, Charles A (2002) Cell surface carbohydrates reveal heterogeneity in olfactory receptor cell axons in the mouse. Cell Tissue Res 308:7-17
Lipscomb, Brian W; Treloar, Helen B; Greer, Charles A (2002) Novel microglomerular structures in the olfactory bulb of mice. J Neurosci 22:766-74
Zou, Dong-Jing; Greer, Charles A; Firestein, Stuart (2002) Expression pattern of alpha CaMKII in the mouse main olfactory bulb. J Comp Neurol 443:226-36
Au, Winnie W; Treloar, Helen B; Greer, Charles A (2002) Sublaminar organization of the mouse olfactory bulb nerve layer. J Comp Neurol 446:68-80
Bartolomei, J C; Greer, C A (2000) Olfactory ensheathing cells: bridging the gap in spinal cord injury. Neurosurgery 47:1057-69

Showing the most recent 10 out of 12 publications