SMALL SUBCLASS OF RAT OLFACTORY NEURONS WITH SPECIFIC BULBAR PROJECTIONS IS REACTIVE WITH MONOCLONAL-ANTIBODIES TO THE HSP70 HEAT-SHOCK PROTEIN

As part of a study of turnover of rat olfactory receptor neurons we ha ve been examining immunohistochemical expression of members of the 70 kD heat shock protein (HSP70) family in the olfactory epithelium. Expr ession of HSP70 family members is up-regulated in many cells following exposure to physiologically stressing conditions. Because dying neuro ns are likely to undergo some sort of physiological stress before the onset of frank degeneration, we hoped that anti-HSP70 monoclonal antib odies would prove to be useful markers for early stages of olfactory n euron cell death. Two anti-human HSP70 monoclonal antibodies were used , Mabs 2A4 and 3a3. Two-dimensional gel electrophoresis/western blot a nalysis indicates that these Mabs are reactive with the HSC70 and HSP7 0 members of the rat HSP70 family. Immunohistological observations sho w that both Mabs are strongly reactive with a widely dispersed subpopu lation of olfactory receptor neurons. Morphological, immunohistologica l, and autoradiographic birthdating analyses demonstrate that reactive cells are fully mature receptor neurons. Their reactivity, however, d oes not appear to be stress-related More significantly, axons of react ive neurons show intense anti-2A4 reactivity. This has allowed us to t race these axons to their target glomeruli in the olfactory bulb, demo nstrating that the reactive neurons project to just one to two glomeru li on either side of each bulb via consistent and predictable pathways . This is the first subpopulation of olfactory receptor neurons to be traced to such a small number of glomeruli. Given this extremely small number, it seems likely that the reactive receptor cell subpopulation serves some specific olfactory function. In addition, axonal 2A4 reac tivity should also prove useful in defining the relative roles of rece ptor neurons and glomeruli in the establishment of epithelial-glomerul ar connections. (C) 1994 Wiley-Liss, Inc.