The proposed research is aimed at characterizing a specialized subset of neurons in the olfactory epithelium. These D neurons appear to be unique in expressing a novel signal transduction pathway (guanylyl cyclase, GC- D) among olfactory receptor cells. These neurons may also be involved in mediating suckling behavior in neonatal rodents. The applicant proposes to: 1) isolate D neurons and characterize the signal transduction pathway and receptor molecules expressed in these cells; 2) show that GC-D is necessary for the normal expression of tyrosine hydroxylase (TH) in the olfactory bulbs, as an indicator of afferent activity; 3) examine the projection patterns of D neurons; and 4) show that GC-D neurons are necessary for nipple attachment and suckling in neonatal mice.
These aims are related in an attempt to associate a specific subset of olfactory receptor cells, with unique signal transduction, to a particular set of neonatal behaviors. GC-D knockout/knockin mice will be generated to carry out the proposed experiments to identify D neurons, which make up less than 1% of olfactory receptor cells. A variety of molecular biological techniques will be used to screen isolated D neurons for the receptors and signal transduction components and use histochemical techniques for identifying projection patterns of D neurons and TH in the olfactory bulbs. In addition, GC-D transgenic mice will be used to examine the ability of neonates to attach to nipples and suckle.
| 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 |
| Zufall, F; Munger, S D (2001) From odor and pheromone transduction to the organization of the sense of smell. Trends Neurosci 24:191-3 |
