Focal denervation alters cellular phenotypes and survival in the developing rat olfactory bulb

Several studies have demonstrated that contact between the olfactory nerve and the forebrain is critical for normal olfactory bulb development. Removal of the embryonic olfactory placode results in a failure of the olfactory bulb to form, as well as causing other forebrain malformations. The current study introduces a technique that permits removal of contact between specific regions of the olfactory nerve and the bulb early in development, without causing damage to other brain regions, and without removing the peripheral olfactory organ. The manipulation, which involves insertion of a small Teflon chip between the cribriform plate and the bulb, prohibits growth of new axons into the "shadow" region behind the implant. Focal denervation of the olfactory bulb causes a decrease in bulb and layer sizes, a reduction in mitral cell number, and changes to bulb architecture. Using a battery of antibodies (OMP, MAP2, TuJ1, calretinin, calbindin, parvalbumin, TH, and GAD), we further demonstrated that 1) focal denervation alters the relationship between the olfactory nerve and the bulb, 2) the fine structure of cells in denervated regions is disrupted, and 3) cellular phenotypes change in response to loss of afferent contact. These results suggest that contact between the olfactory nerve and the bulb is important for maintaining bulb architecture and cell survival, structure, and phenotype. They also point to focal denervation as a useful technique for examining the role of neural contact in olfactory development and maintenance of the central nervous system.