Guthrie, Kathleen M.

Unlike most neurons in the adult nervous system, olfactory receptor neurons (ORN),
found in the olfactory epithelium (OE), continually turnover in the adult rat. These
neurons project their axons to the olfactory bulb which is their central target. The
present study eliminated target neurons in the bulb using N-methyl-D-aspartate
(NMDA) to examine the effects of target loss on ORN survival and maturation. We
compared the effects of the NMDA lesion to bulbectomy, a permanent surgical
removal of the bulb, which simultaneously causes damage to ORN axons. We found
that unlike bulbectomy, large numbers of dying OE cells were not observed at any
time after the lesion. The number of immature neurons increased relative to the
control side, and the number of mature neurons also slightly increased with time
following NMDA lesion. Survival of ORNs does not seem to be significantly altered
in the absence of its target.

It is of interest to understand how new neurons incorporate themselves into the
existing circuitry of certain neuronal populations. One such population of neurons is that
which are born in the subventricular zone (SVZ) and migrate to the olfactory bulb where
they differentiate into granule cells. Another area of interest is the role of brain-derived
neurotrophic factor (BDNF) on the survival and overall health of these neurons. This
study aimed to test whether or not BDNF is a survival factor for adult-born granule cells.
Here were utilized a transgenic mouse model over-expressing BDNF under the α-
calcium/calmodulin-dependent protein kinase II (CAMKIIα) promoter, and tested its
effect on olfactory granule cells under sensory deprived conditions. Results from this
experiment indicated that there was no significant difference in cell death or cell survival when comparing transgenic and wild type animals. We concluded that BDNF is not a
survival factor for adult-born granule cells.

The adult rodent olfactory system provides an excellent model for the study of the
developing nervous system due to its constant integration of new neurons and
establishment of new synapses throughout life. This allows for adaptive structural
responses to sensory experience that continuously shape functional circuits to fit the
behavioral needs of the animal. The cellular mechanisms underlying the anatomical
plasticity of the adult olfactory system are not well understood, but neurotrophins, long
recognized as crucial to the early development of neuronal circuits, are attractive
candidate molecules in this capacity. Brain-derived neurotrophic factor (BDNF) and
nerve growth factor (NGF), two members of the neurotrophin family, have received
attention in terms of their anatomical distribution and physiological functions in the olfactory system.

Olfactory sensory neurons (OSN) expressing the same odor receptor (OR) project their axons to topographically fixed glomeruli in the olfactory bulb (OB). This topographic map results from axon guidance mechanisms determined by ORs, glia and molecular guidance cues. The present study examined the organization of mature OSNs expressing the P2 OR in adult mice after ablation of bulb neurons with N-methyl-D-aspartate (NMDA). Rapid neuronal degeneration was followed by progressive laminar disorganization of the OB and glomerular shrinkage. P2 axon targeting and convergence was maintained within degenerating glomeruli for up to 2 weeks. After that time, fewer P2 axons were observed in the lesioned OB with fewer P2 neurons in the olfactory epithelium (OE). By 3 weeks, the mature OSN population was reduced and the immature population was increased. These results suggest that bulbar synaptic contacts do not maintain sensory axon convergence in the adult, but regulate neuronal survival in the OE.