The cascade of mechanisms that regulate the outgrowth of axons from olfactory sensory neurons (OSNs) and their precise targeting to specific glomeruli in the olfactory bulb remain controversial. While the odor receptors expressed by the OSNs are strongly implicated, there are conflicting reports pertaining to the functional transduction cascade downstream from the odor receptors. An absence of functional activity induced by naris closure, or deletion of a member of the transduction cascade, adenylyl cyclase 111, can have significant effects on the organization of OSN axons and their target glomeruli. However, perturbation of the cyclic nucleotide gated (CNG) channel that is the target of cAMP within the cascade results in little perturbation of axon outgrowth/targeting. Recent findings suggested that cAMP may contribute to OSN axon outgrowth, independent of CNG channel opening, by entering the nucleus and regulating gene expression. My goal is to explore an alternative hypothesis: that 1(h), the current generated by), contributes to OSN depolarization/ excitation and in the absence of the CNG channel can underlie axon outgrowth, coalescence, and formation of glomeruli. I propose a series of studies that will establish the spatio-temporal framework of HCN subunit expression, quantify developmental transients in subunit expression, directly test the effect of HCN on axon outgrowth and branching, and finally, explore how the absence of the HCN1 subunit affects OSN convergence and targeting. The data will have significant implications for developmental disorders such as Kallman's syndrome, and more generally for understanding developmental dynamics and cell-cell interactions during the initial development of sensory systems.
| Mobley, Arie S; Bryant, Alex K; Richard, Marion B et al. (2013) Age-dependent regional changes in the rostral migratory stream. Neurobiol Aging 34:1873-81 |
| Mobley, Arie S; Miller, Alexandra M; Araneda, Ricardo C et al. (2010) Hyperpolarization-activated cyclic nucleotide-gated channels in olfactory sensory neurons regulate axon extension and glomerular formation. J Neurosci 30:16498-508 |
