Neural regeneration and the peripheral olfactory system

The peripheral olfactory system is able to recover after injury, i.e., the olfactory epithelium reconstitutes, the olfactory nerve regenerates, and the olfactory bulb is reinnervated, with a facility that is unique within the mammalian nervous system. Cell renewal in the epithelium is directed to replace neurons when they die in normal animals and does so at an accelerated pace after damage to the olfactory nerve. Neurogenesis persists because neuron-competent progenitor cells, including transit amplifying and immediate neuronal precursors, are maintained within the population of globose basal cells. Notwithstanding events in the neuron-depleted epithelium, the death of both non-neuronal cells and neurons directs multipotent globose basal cell progenitors, to give rise individually to sustentacular cells and horizontal basal cells as well as neurons. Multiple growth factors, including TGF-alpha, FGF2, BMPs, and TGF-betas, are likely to be central in regulating choice points in epitheliopoiesis. Reinnervation of the bulb is rapid and robust. When the nerve is left undisturbed, i.e., by lesioning the epithelium directly, the projection of the reconstituted epithelium onto the bulb is restored to near-normal with respect to rhinotopy and in the targeting of odorant receptor-defined neuronal classes to small clusters of glomeruli in the bulb. However, at its ultimate level, i.e., the convergence of axons expressing the same odorant receptor onto one or a few glomeruli, specificity is not restored unless a substantial number of fibers of the same type are spared. Rather, odorant receptor-defined subclasses of neurons innervate an excessive number of glomeruli in the rough vicinity of their original glomerular targets.