Odorant Receptor Expression Patterns Are Restored in Lesion-Recovered Rat Olfactory Epithelium

Abstract

Lesions of the olfactory periphery provide a means for examining the reconstitution of a diverse and highly regulated population of sensory neurons and the growth, en masse, of nascent axons to the bulb. The olfactory epithelium and its projection onto the bulb are reconstituted after ablation by methyl bromide gas, and some measure of olfactory function is restored. The extent to which the system regenerates the full repertoire of odorant receptor-expressing neurons, particularly their spatially restricted distribution across the epithelial sheet, is unknown, however, and altered odorant receptor expression might contribute to the persistent distortion of odorant quality that is observed in the lesioned-recovered animals. To address the question of receptor expression in the recovered epithelium, we performed in situ hybridization with digoxigenin-labeled riboprobes for eight odorant receptors on the olfactory epithelium from unilaterally methyl bromide-lesioned and control rats. The data demonstrate that the distribution of sensory neuron types, as identified and defined by odorant receptor expression, is restored to normal or nearly so by 3 months after lesion. Likewise, the numbers of probe-labeled neurons in the lesioned-recovered epithelium are nearly equivalent to the unlesioned side at this time. Finally, our evidence suggests that odorant receptors are distributed in multiple overlapping bands in the normal, unlesioned, and lesioned-recovered epithelium rather than in the conventionally accepted three or four zones. Thus, the primary sensory elements required for functional recovery of the olfactory system after damage are restored, and altered function implies the persistence of a more central failure in regeneration.

Differential development of odorant receptor expression patterns in the olfactory epithelium: A quantitative analysis in the mouse septal organ

“…Similar regulation may also occur during regeneration after lesion to the olfactory epithelium, because the recovered OR expression pattern closely resembles that in the control animals (Iwema et al, 2004). The developmental trajectories of the OR expression patterns may be modified by the postnatal (or even prenatal) chemical environment.…”

Localization of eNOS in the Olfactory Epithelium of the Rat

“…There is one possibility that these results are correlated with the localization of particular olfactory receptors. It has been reported that several olfactory receptors were expressed in the restricted region of the rat nasal cavity [24,42], and that olfactory receptors OR14 and OR16 were expressed in the olfactory epithelium lining dorsomedial region of the rat nasal cavity [24]. Therefore, eNOS protein may be expressed more intensely in the olfactory cells expressing OR14 and OR16 than in those cells expressing other receptors.…”

β1,3-N-Acetylglucosaminyltransferase 1 Glycosylation Is Required for Axon Pathfinding by Olfactory Sensory Neurons

“…These observations are relevant to the recovery of individual neuronal populations observed in ␤3GnT1 null mice, in which, despite the widespread reexpression of lactosamine, the population of P2 and I7 odorant receptor neurons decreased postnatally until Ͻ15% of the normal number remained in adults. One possibility is that variations in sensory experience attributable to differences in environmental odor ligand exposure could lead to variations in recovery, a hypothesis previously suggested from chemical lesioning models of olfactory regeneration (Iwema et al, 2004). It is also possible that some subsets of sensory neurons are unable to de novo express lactosamine during the regeneration phase.…”

“…Digoxigenin-labeled riboprobes (Roche Applied Science, Indianapolis, IN) were synthesized and hybridized to 4% paraformaldehyde-fixed, cryosectioned tissue as described previously (Henion et al, 2001). Odorant receptor riboprobes, prepared according to Iwema et al (2004), were provided by Dr. James Schwob (Tufts University, Boston, MA).…”