Abstract
BackgroundOne of the fundamental questions in olfaction is whether olfactory receptor neurons (ORNs) behave as independent entities within the olfactory epithelium. On the basis that mature ORNs express multiple connexins, I postulated that gap junctional communication modulates olfactory responses in the periphery and that disruption of gap junctions in ORNs reduces olfactory sensitivity. The data collected from characterizing connexin 43 (Cx43) dominant negative transgenic mice OlfDNCX, and from calcium imaging of wild type mice (WT) support my hypothesis.ResultsI generated OlfDNCX mice that express a dominant negative Cx43 protein, Cx43/β-gal, in mature ORNs to inactivate gap junctions and hemichannels composed of Cx43 or other structurally related connexins. Characterization of OlfDNCX revealed that Cx43/β-gal was exclusively expressed in areas where mature ORNs resided. Real time quantitative PCR indicated that cellular machineries of OlfDNCX were normal in comparison to WT. Electroolfactogram recordings showed decreased olfactory responses to octaldehyde, heptaldehyde and acetyl acetate in OlfDNCX compared to WT. Octaldehyde-elicited glomerular activity in the olfactory bulb, measured according to odor-elicited c-fos mRNA upregulation in juxtaglomerular cells, was confined to smaller areas of the glomerular layer in OlfDNCX compared to WT. In WT mice, octaldehyde sensitive neurons exhibited reduced response magnitudes after application of gap junction uncoupling reagents and the effects were specific to subsets of neurons.ConclusionsMy study has demonstrated that altered assembly of Cx43 or structurally related connexins in ORNs modulates olfactory responses and changes olfactory activation maps in the olfactory bulb. Furthermore, pharmacologically uncoupling of gap junctions reduces olfactory activity in subsets of ORNs. These data suggest that gap junctional communication or hemichannel activity plays a critical role in maintaining olfactory sensitivity and odor perception.
Highlights
One of the fundamental questions in olfaction is whether olfactory receptor neurons (ORNs) behave as independent entities within the olfactory epithelium
PCR amplification of reverse transcription products using a primer pair spanning the regions encoding for the two proteins fused in the construct (Cx43 and b-gal) showed a single band at the estimated size in OlfDNCX but not in wild type mice (WT) (Figure 2A)
The olfactory responses of ethyl acetate and heptaldehyde were lower in OlfDNCX compared to WT, when they were normalized to those of benzaldehyde
Summary
One of the fundamental questions in olfaction is whether olfactory receptor neurons (ORNs) behave as independent entities within the olfactory epithelium. Subsequent studies further demonstrate that ORN input is responsible for, or partially responsible for, the diverse spatial and temporal dynamics observed in glomeruli [5,6] These results are in sharp contrast to those from single isolated ORNs in which the dose-response relationships are typically saturated within a log unit [7,8]. I present data to demonstrate that impairment of gap junctions or altered assembly of gap junctions or hemichannels in ORNs modulates odor responsiveness and leads to changes in olfactory activation patterns in the olfactory bulb. My study suggests that coordination of neuronal activity between ORNs through gap junctions or hemichannels may constitute an important mechanism in modulating olfactory sensitivity and odor perception
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