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.