Neurogenesis in olfactory epithelium: loss and recovery of transepithelial voltage transients following olfactory nerve section.

1. Unilateral olfactory nerve section was performed on the salamander, Ambystoma tigrinum. Physiological recordings and macroscopic observations were made to investigate the physiological correlates of functional recovery in the olfactory epithelium. 2. Slow transepithelial voltage transients, Veog, evoked by several odorous stimuli systematically decreased in amplitude during the initial 7 days and were not recorded at 10 days following nerve section, suggesting retrograde degeneration of receptor neurons. This was true for negative Veog(-), and positive, Veog(+), response components. Responses obtained from the untreated contralateral side of each animal remained similar to nonaxotomized controls. 3. Progressive recovery of the voltage transients was studied at 24, 45, 80, and 100 days following nerve section. At all stages of recovery, the wave form and time course of the responses were characteristic for each stimulus. This suggested that the response properties of the newly differentiated neuronal population were similar to those of the mature population. 4. At 100 days, response amplitudes evoked by all stimuli were similar to control values at all recording sites on the epithelial surface. The simultaneous loss and recovery of positive and negative components of the Veog indicated that the sources of both are dependent on the presence of functionally mature olfactory receptor neurons. 5. Visual inspection indicated that the olfactory nerve was reconstituted and reconnected to the olfactory bulb between 30-60 days following transection. The fact that physiological activity was recorded in the epithelium prior to this event suggests that molecular recognition and sensory transduction are not dependent on connectivity with the olfactory bulb. 6. It is concluded that physiological recovery of the olfactory receptor cell population occurs following axotomy. The time course of recovery was consistent with morphological evidence (see Ref. 57), indicating that newly differentiated receptor neurons are derived from cells in the basal region of the epithelium and replace the population lost through retrograde degeneration.