LOCALIZATION AND REGULATION OF LOW-AFFINITY NERVE GROWTH-FACTOR RECEPTOR EXPRESSION IN THE RAT OLFACTORY SYSTEM DURING DEVELOPMENT AND REGENERATION

Nerve growth factor (NGF), a classic neurotrophic factor, promotes neu ronal survival, maintenance, regeneration and differentiation in the p eripheral nervous system and parts of the central nervous system. NGF activity is mediated by cell surface bound receptors including the low affinity NGF receptor (LNGFr) which is expressed by some peripheral a nd central neurons and is present on peripheral nerve Schwann cells du ring development and regeneration. The olfactory system is a useful mo del for the study of the role of LNGFr in neuronal development and reg eneration. The growth of olfactory axons into the brain begins in the embryo and continues through the first few postnatal weeks. In mature animals there is persistent turnover and generation of olfactory recep tor neurons (ORNs) and continuous growth of new axons into the olfacto ry bulb. These new axons grow along the preexisting olfactory pathway. In the mature olfactory system, LNGFr has been observed in the glomer ular layer of the olfactory bulb, the target of ORNs. However, neither the cellular localization nor the developmental expression of LNGFr h as been characterized. Here, we tested the hypothesis that LNGFr expre ssion is developmentally regulated in the olfactory nerve and is reind uced following injury to the mature olfactory nerve. LNGFr-immunoreact ivity (IR) was first observed in the olfactory mucosa at embryonic day (E)13 and in the olfactory nerve at E14. LNGFr-IR increased in the ne rve during embryonic development, began to decrease at around postnata l day (P)5 and was scarcely detectable in normal adults. The staining pattern suggests that LNGFr is located on the olfactory nerve Schwann cells. Streaks of LNGFr-IR were present in the adult olfactory nerve. We reasoned that these streaks might represent transient reexpression of LNGFr associated with normal olfactory neuron turnover and replacem ent. Consistent with this hypothesis, LNGFr was robustly reexpressed i n the adult olfactory nerve following lesion of the olfactory epitheli um. Starting late in development (E21) and in the adult, LNGFr-IR was also observed on fibers in deep layers of the olfactory bulb. LNGFr-IR was also observed in neurons of the nucleus of the diagonal band (NDB ) in the basal forebrain. NDB is the sole source of cholinergic affere nts of the olfactory bulb. Thus, we tested the hypothesis that LNGFr i n the deep layers of the olfactory bulb is located on NDB axons by mak ing lesions of NDB. Following the lesion, LNGFr-IR disappeared in the deep layers of the olfactory bulb but remained in the glomerular layer . We conclude that LNGFr-IR is associated with several distinct popula tions of cells in the olfactory system. This suggests that LNGFr-IR pl ays several distinct functional roles in the olfactory system, includi ng support of olfactory axon growth and regeneration and maintenance o f cholinergic innervation of the olfactory bulb. (C) 1994 Wiley-Liss, Inc.