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Gap junctions in olfactory neurons modulate olfactory sensitivity.

Zhang C - BMC Neurosci (2010)

Bottom Line: Electroolfactogram recordings showed decreased olfactory responses to octaldehyde, heptaldehyde and acetyl acetate in OlfDNCX compared to WT.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biological, Chemical and Physical Sciences, Illinois Institute of Technology, Chicago, IL 60616, USA. zhangc@iit.edu

ABSTRACT

Background: One 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.

Results: I 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.

Conclusions: My 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.

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OlfDNCX mice exhibit a reduced glomerular activity map to octaldehyde. A and B. Pseudocolor contour maps showing averaged octaldehyde-evoked glomerular activation patterns in wild type mice (A) and their OlfDNCX littermates (B) (n = 8 for each map). The color denotes the number of activated glomeruli in a region spanning 216 μm in the rostrocaudal direction and 30 degrees in the angle dimension. The pseudocolor scale varies linearly from blue (0 glomerulus) to red (16 glomeruli). C. p values for a pixel by pixel Mann-Whitney test of differences between the odor maps in (A) and (B). Areas enclosed by black contour lines are regions that differ significantly (p < 0.006). The pseudocolor scale varies logarithmically from a p value of 0.5 (blue) to 10-5 (red). D. A diagram indicating the locations of domains that differ between OlfDNCX and wild type mice.
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Figure 5: OlfDNCX mice exhibit a reduced glomerular activity map to octaldehyde. A and B. Pseudocolor contour maps showing averaged octaldehyde-evoked glomerular activation patterns in wild type mice (A) and their OlfDNCX littermates (B) (n = 8 for each map). The color denotes the number of activated glomeruli in a region spanning 216 μm in the rostrocaudal direction and 30 degrees in the angle dimension. The pseudocolor scale varies linearly from blue (0 glomerulus) to red (16 glomeruli). C. p values for a pixel by pixel Mann-Whitney test of differences between the odor maps in (A) and (B). Areas enclosed by black contour lines are regions that differ significantly (p < 0.006). The pseudocolor scale varies logarithmically from a p value of 0.5 (blue) to 10-5 (red). D. A diagram indicating the locations of domains that differ between OlfDNCX and wild type mice.

Mentions: When mice were exposed to fresh air passing through a vessel with 0.001% octaldehyde in odorless mineral oil, a moderate intensity stimulus known to be detectable by mice (Slotnick, Zhang and Restrepo, unpublished), odor-evoked c-fos mRNA expression was elevated in juxtaglomerular cells in discrete areas. Figure 5 shows the odor maps of averaged glomerular activation evoked by exposure to octaldehyde in WT (Figure 5A) and OlfDNCX mice (Figure 5B). The areas of maximal activation in the ventral zone (shown in yellow and red in the figure) overlap. However, consistent with the decreased responsiveness of the olfactory epithelium to octaldehyde in the EOG experiments, overall levels of activation were lower for OlfDNCX. In OlfDNCX, a total number of 458 ± 25.5 glomeruli were activated, while the number of glomeruli activated by octaldehyde in WT was 620 ± 59.5 (mean ± SE, n = 8 for each group, p < 0.05). In order to explore regional differences in glomerular activation, I used a point by point Mann-Whitney test with confidence interval p values corrected for multiple comparisons using the false discovery rate procedure [45,48,49]. The areas within the black contour lines of Figure 5C were statistically different. There were regions, particularly in the ventromedial, medial and caudolateral areas where the number of glomeruli activated by octaldehyde was substantially smaller for OlfDNCX compared to WT.


Gap junctions in olfactory neurons modulate olfactory sensitivity.

Zhang C - BMC Neurosci (2010)

OlfDNCX mice exhibit a reduced glomerular activity map to octaldehyde. A and B. Pseudocolor contour maps showing averaged octaldehyde-evoked glomerular activation patterns in wild type mice (A) and their OlfDNCX littermates (B) (n = 8 for each map). The color denotes the number of activated glomeruli in a region spanning 216 μm in the rostrocaudal direction and 30 degrees in the angle dimension. The pseudocolor scale varies linearly from blue (0 glomerulus) to red (16 glomeruli). C. p values for a pixel by pixel Mann-Whitney test of differences between the odor maps in (A) and (B). Areas enclosed by black contour lines are regions that differ significantly (p < 0.006). The pseudocolor scale varies logarithmically from a p value of 0.5 (blue) to 10-5 (red). D. A diagram indicating the locations of domains that differ between OlfDNCX and wild type mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2944353&req=5

Figure 5: OlfDNCX mice exhibit a reduced glomerular activity map to octaldehyde. A and B. Pseudocolor contour maps showing averaged octaldehyde-evoked glomerular activation patterns in wild type mice (A) and their OlfDNCX littermates (B) (n = 8 for each map). The color denotes the number of activated glomeruli in a region spanning 216 μm in the rostrocaudal direction and 30 degrees in the angle dimension. The pseudocolor scale varies linearly from blue (0 glomerulus) to red (16 glomeruli). C. p values for a pixel by pixel Mann-Whitney test of differences between the odor maps in (A) and (B). Areas enclosed by black contour lines are regions that differ significantly (p < 0.006). The pseudocolor scale varies logarithmically from a p value of 0.5 (blue) to 10-5 (red). D. A diagram indicating the locations of domains that differ between OlfDNCX and wild type mice.
Mentions: When mice were exposed to fresh air passing through a vessel with 0.001% octaldehyde in odorless mineral oil, a moderate intensity stimulus known to be detectable by mice (Slotnick, Zhang and Restrepo, unpublished), odor-evoked c-fos mRNA expression was elevated in juxtaglomerular cells in discrete areas. Figure 5 shows the odor maps of averaged glomerular activation evoked by exposure to octaldehyde in WT (Figure 5A) and OlfDNCX mice (Figure 5B). The areas of maximal activation in the ventral zone (shown in yellow and red in the figure) overlap. However, consistent with the decreased responsiveness of the olfactory epithelium to octaldehyde in the EOG experiments, overall levels of activation were lower for OlfDNCX. In OlfDNCX, a total number of 458 ± 25.5 glomeruli were activated, while the number of glomeruli activated by octaldehyde in WT was 620 ± 59.5 (mean ± SE, n = 8 for each group, p < 0.05). In order to explore regional differences in glomerular activation, I used a point by point Mann-Whitney test with confidence interval p values corrected for multiple comparisons using the false discovery rate procedure [45,48,49]. The areas within the black contour lines of Figure 5C were statistically different. There were regions, particularly in the ventromedial, medial and caudolateral areas where the number of glomeruli activated by octaldehyde was substantially smaller for OlfDNCX compared to WT.

Bottom Line: Electroolfactogram recordings showed decreased olfactory responses to octaldehyde, heptaldehyde and acetyl acetate in OlfDNCX compared to WT.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biological, Chemical and Physical Sciences, Illinois Institute of Technology, Chicago, IL 60616, USA. zhangc@iit.edu

ABSTRACT

Background: One 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.

Results: I 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.

Conclusions: My 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.

Show MeSH
Related in: MedlinePlus