The primary olfactory projection has two chemically distinct zones.

The sensory neurons of the olfactory epithelium form an anatomically uniform population but are differentially excited by odorants. We have discovered an unexpected biochemical heterogeneity within this population that extends to its axonal projection onto the olfactory bulb. This heterogeneity is recognized by a newly generated monoclonal antibody, designated RB-8, that differentially stains the primary olfactory projection in rats and divides it into 2 nonoverlapping zones. With light-microscopic immunohistochemistry, RB-8 densely labels the fascicles of the olfactory nerve from the ventral and lateral parts of the olfactory epithelium, where there is also some epithelial staining. This area, which we designate RB-8-positive, comprises about two-thirds of the epithelial sheet. RB-8 labeling of the other third of the epithelium, which includes the dorsal recess and medial tips of the dorsal turbinals, is not detectable, and the fascicles from these RB-8-negative areas are only weakly stained. These RB-8-negative areas form a contiguous zone on flattened maps of the epithelial sheet. In the olfactory bulb, RB-8 staining of the glomeruli in the ventrolateral part is correspondingly dense, while that in the dorsomedial glomeruli is undetectable or very light. In the labeled glomeruli, the RB-8 staining is precisely coextensive with anti-olfactory marker protein staining, which serves as a marker for the olfactory axons and terminals. In addition, knife-cut lesions of the olfactory nerve totally eliminate the RB-8 staining in the glomeruli where the destruction of the olfactory terminals is complete. There is also a good correlation between the staining patterns in the bulb and epithelium and what is known from tract-tracing studies of the arrangement of the axonal projection of the epithelium onto the bulb. This evidence strongly suggests that, in the olfactory nerve and glomeruli, RB-8 stains the olfactory axons and their terminals. A survey of the CNS and peripheral tissues demonstrates that staining with RB-8 is nervous system-specific; not all components of the CNS and PNS are stained. The antigen recognized by RB-8 was characterized in immunoblots and by use of a direct radioimmunoassay (RIA) which assessed binding of 125I-RB-8. With this assay, the RB-8 binding sites in whole brain are shown to be membrane-associated, saturable, immunologically specific for RB-8, and trypsin-sensitive. In SDS-PAGE immunoblots of membrane proteins, the antigen in rat forebrain and in the olfactory nerve is a protein of 125 kDa Mr, which comigrates in mixtures of membranes from the 2 sources.(ABSTRACT TRUNCATED AT 400 WORDS)