June 1997

" Plasticity and potential development

of the olfactory organ "

by Pasquale Graziadei

Distinguished Research Professor, Emeritus

Florida State University, Tallahassee, FL 32312 - USA

The olfactory organ has been for a long time neglected by the classic neurobiologists, attracted by the more complex intricacies and the volume of the brain and spinal cord. The intrinsic simplicity of the olfactory epithelium and its direct connections with the brain as well as the not obvious importance of the organ as a whole in the behavior of the humans, allowed for a justifiable neglect. Serendipidy and a degree of ingenuity accounted for a reversal of fortunes in the interest devoted to the olfactory organ, which has became recently what we would call a "hot topic" among neurobiologists.

In recent years it has been ascertained that the olfactory neurons are unique among nerve cells of adult vertebrates, (among them primates and humans), in their capacity to replace themselves from the olfactory neuroblasts (their precursors which persist into adulthood) and actually undergo a turnover. This is in stark contrast with the other neurons of our nervous system, which lose the capacity to be replaced after birth due to the lack of their precursors. This exceptional ability of the olfactory neurons to renew themselves has given to the neurobiologist unexpected possibilities of experimentation.

It has thus been found out in mammals that the regrowing olfactory nerve, originated from the reconstituded olfactory nervous, can invade other targets besides its own olfactory bulb (the normal site of termination of the olfactory axons) and in the new location these axons modify the brain allowing the transformation of the preexisting structures in ways reminiscent of olfactory centers. In lower vertebrates the changes are more astonishing. The regrowth of the olfactory nerve influences the structure of the brain " in toto " and the transplant of a supernumerary olfactory organ produces a new brain hemisphere. We have thus observed that in frog embryos the removal of one olfactory organ produces a frog with one hemisphere instead of the normal two, but the transplant of a supernumerary placode results, surprisingly, in a frog with three hemispheres. If the frog is totally deprived of olfactory organs the result is an animal which lacks completely the forebrain (the anterior portion of our brain).

The above mentioned experiments have dramatic theoretical value but are of no direct practical importance to humans, if not for pointing up to characteristics previously unsuspected of the olfactory neuroblasts (the cells that give origin to the olfactory neurons). In fact the experiments on the frogs indicated that when an olfactory organ is transplanted in frog embryos, cells of the organ, the olfactory neuroblasts, migrate to the brain where they become incorporated. This observation, clearly pointing out to the capacity of the olfactory neuroblasts to become cells of the brain, prompted the implementation of a similar experiment in mammals.

The olfactory mucosa of the rats was isolated, its cells were dissociated and among them olfactory neuroblasts, and after purification they were injected in sterile conditions in young and adult rats in diverse brain location. These cells , properly marked to allow secure recognition, were traced into the brain at a distance of a few days to up 45 days. It has been observed that, according to the location, these cells assumed the characteristics of the host's neurons. This discovery would allow for the substitution of lost neurons, if the experiments are positive in humans. More experiments need to be conducted and more tests certainly are warranted, but the possibility exists that one day we can substitute for the missing nerve cells of our brain with material coming from our own body (the olfactory mucosa). The antique prediction that

the nose knows

may at least be true: the organ could not only be an ornament to our face but it could save our brain from the irreparable damage of what it was throught to be a permanent loss, the loss of our nerve cells.

Suggested further reading:

Graziadei P.P.C. and Metcalf J.F. - Autoradiographic and ultrastructural observations on the frog olfactory mucosa - in: Z. Zellforsch. 116 (1971), 305 - 318

Graziadei P.P.C. - Olfactory Development - in: J. R. Coleman (Ed.) Development of Sensory Systems in Mammals. Wiley, New York, 1990, pp. 519 - 566

Koo E. Y. and Graziadei P.P.C. - Cell migration from the transplanted olfactory placode in Xenopus - in: Anat. Embryol. 191 (1995), 171 - 181

Magrassi L. and Graziadei P.P.C. - Lineage specification of olfactory neural precursors depends on continous cell interaction - in: Dev. Brain Res. 96 (1996), 11 - 27

Walker,M.M., Diebel, C.E., Haugh, C.V., Pankhurst, P.M., Montgomery, J.C. & Green, C.R. - Structure and function of the vertebrate magnetic sense - in: Nature 390 (1997), 371