The dynamics of cell genesis in the olfactory epithelium of the adult mouse were investigated using 3H-thymidine autoradiography. Mice were injected once with 3H-thymidine, and their olfactory epithelia were examined 7, 14, 30, 60, and 90 d later. The number of silver grains over each nucleus was counted, and the relative distance from the basement membrane was measured for each labeled nucleus. At 7 and 14 d, the average number of labeled cells in each section was about 20 per mm. By 30 d, and for the following 60 d, the average number of labeled cells was only about 6 per mm. Thus, most cells labeled by the injection died 2-4 weeks after injection. When the labeled cells were compared by nuclear grain density, time after injection (the "survival period"), and distance of the nucleus from the basement membrane (the "migration distance"), it was apparent that there was a small population of "nonmigrating" cells that remained close to the basement membrane. These cells, at first heavily labeled, divided a second time about 60 d after the 3H-thymidine injection, indicated by a significant decrease in nuclear grain density. This nonmigrating, slowly dividing basal cell is probably the neural stem cell, which gives rise to another stem cell and an olfactory neuron precursor by an asymmetric division. When the relative numbers of nonmigrating and migrating cells were compared, the results indicated that, after the asymmetric division, there are at least 2 or 3 rapid, symmetric divisions of the precursor cells, producing many immature receptor cells. Most of these die within 4 weeks of the 3H-thymidine injection.(ABSTRACT TRUNCATED AT 250 WORDS)

The life span of olfactory receptor neurons was investigated after injection of a retrograde tracer into the olfactory bulb. Mice were injected unilaterally with colloidal gold conjugated with Concanavalin A and their olfactory epithelia were examined after 7, 14, 30, 60, and 90 days. Gold particles could be seen in the epithelia at all survival periods after silver intensification. There was no gold in the epithelia on the uninjected side. In order to test whether gold could be recycled within the epithelium upon the death of receptor neurons, the olfactory bulbs of some mice were ablated 4 days after colloidal gold injection. None of the receptor neurons in these epithelia contained gold at any survival period. To investigate whether gold was continuously available at the injection site, olfactory bulbs were examined by electron microscopy. By 7 days after injection all gold was sequestered intracellularly and was presumably unavailable for uptake by the olfactory axons. These results indicate that olfactory receptor neurons live for at least three times the commonly accepted life span of 30 days. A long life span challenges the widely held view that olfactory receptor neurons are regularly replaced.