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Zonal ablation of the olfactory sensory neuroepithelium of the mouse: effects on odorant detection.
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). (Berghard)
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). (Berghard)
2004 (English)In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 20, no 7, 1858-1864 p.Article in journal (Refereed) Published
Abstract [en]

Olfactory sensory neurons that express a specific odorant receptor, out of a thousand different, are unevenly distributed within, but restricted to one of four zones of the neuroepithelial sheet in the nasal cavity in the mouse. This zonal restriction of neurons expressing the same odorant receptor may have consequences, e.g. in case of localized injury. We found that the chemical dichlobenil can produce specific and permanent ablation of neurons in odorant receptor expression zone 1, while a higher dichlobenil dose causes reversible toxicity in neighboring zones. In behavior tests, mice lacking part of the olfactory epithelium had an increased detection threshold concentration of two-four orders of magnitude for some odorants but not others, resembling the phenomenon of specific hyposmia. This indicates that the broad tuning properties of single odorant receptors and their large number cannot fully compensate for loss of the receptor(s) with the highest sensitivity for a particular odorant.

Place, publisher, year, edition, pages
2004. Vol. 20, no 7, 1858-1864 p.
Keyword [en]
Acetates, Animals, Benzene, Male, Mice, Mice; Inbred C57BL, Odors, Olfactory Mucosa/cytology, Olfactory Receptor Neurons/*physiology, Pyridazines, Smell/*physiology
URN: urn:nbn:se:umu:diva-16662DOI: 10.1111/j.1460-9568.2004.03634.xPubMedID: 15380007OAI: diva2:156335
Available from: 2007-10-08 Created: 2007-10-08 Last updated: 2011-05-26
In thesis
1. Molecular and functional anatomy of the mouse olfactory epithelium
Open this publication in new window or tab >>Molecular and functional anatomy of the mouse olfactory epithelium
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The olfactory system is important for social behaviors, feeding and avoiding predators. Detection of odorous molecules is made by odorant receptors on specialized sensory neurons in the olfactory epithelial sheet. The olfactory sensory neurons are organized into a few regions or “zones” based on the spatially limited expression of odorant receptors. In this thesis the zonal division and functional specificity of olfactory sensory neurons have been studied in the mouse. We find that zones 2-4 show overlapping expression of odorant receptors while the border between the regions that express a zone 1 and a zone 2 odorant receptor, respectively, is sharp. This result indicates that zone 1 and zones 2-4 are inherently different from each other. In cDNA screens, aimed at finding genes whose expression correlate to the zonal expression pattern of odorant receptors, we have identified a number of signaling proteins implicated in neural-tissue organogenesis in other systems. The differential expression pattern of identified genes suggests that regional organization is maintained during the continuous neurogenesis in the olfactory epithelium as a result of counter gradients of positional information. We show that the gene c-fos is induced in olfactory sensory neurons as a result of cell activation by odorant exposure. A zonal and scattered distribution of c-Fos-positive neurons resembled the pattern of odorant receptor expression and a change of odorant results in a switch in which zone that is activated. Whereas earlier studies suggest that the odorant receptors are relatively broadly tuned with regard to ligand specificity, the restricted patterns of c-Fos induction suggests that low concentrations of odorous molecules activate only one or a few ORs. Studies on olfactory detection abilities of mice with zonal-restricted lesions in the olfactory epithelium show that loss of a zone has severe effects on the detection of some odorants but not others. These findings lend support to a hypothesis that odorant receptors are tuned to more limited numbers of odorants. Regional differences in gene expression and differences in response to toxic compounds between the zones indicate that there may be differences in tissue homeostasis within the epithelium. We have found that there are differences in proliferation and survival of olfactory sensory neurons in regions correlating to receptor expression zones. Identified differences with regard to gene expression, tissue homeostasis and odorant detection show that the olfactory epithelium is divided into regions that transduce different stimulus features.

Place, publisher, year, edition, pages
Umeå: Molekylärbiologi, 2006. 71 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1047
olfactory epithelium, odorant receptor, zone, odorant, gene expression, cell specification, c-Fos, dichlobenil, olfactometry, proliferation
National Category
Biochemistry and Molecular Biology
urn:nbn:se:umu:diva-868 (URN)91-7264-138-X (ISBN)
Public defence
2006-10-06, Major Groove, 6L, Umeå Universitet, 901 87 Umeå, 09:30 (English)
Available from: 2006-09-19 Created: 2006-09-19 Last updated: 2009-10-30Bibliographically approved

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Vedin, ViktoriaBerghard, Anna
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Department of Molecular Biology (Faculty of Medicine)Department of Molecular Biology (Faculty of Science and Technology)
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