The Regeneration of P2 Olfactory Sensory Neurons Is Selectively Impaired Following Methyl Bromide Lesion

摘要

The capacity of the peripheral olfactory system to recover after injury has not been thoroughly explored. P2-IRES-tauLacZ mice were exposed to methyl bromide, which causes epithelial damage and kills 90% of the P2 neurons. With subsequent neuronal regeneration, P2 neurons recover within their usual territory to equal control numbers by 1 month but then decline sharply to roughly 40% of control by 3 months. At this time, the P2 projection onto the olfactory bulb is erroneous in several respects. Instead of converging onto 1 or 2 glomeruli per surface, small collections of P2 axons innervate multiple glomeruli at roughly the same position in the bulb as in controls. Within these glomeruli, the P2 axons are aggregated near the edge, whereas the remainder of the glomerulus contains olfactory marker protein (+), non-P2 axons, violating the one receptor-one glomerulus rule normally observed. The aggregates are denser than found in control P2-innervated glomeruli, suggesting that the P2 axons may not be synaptically connected. Based on published literature and other data, we hypothesize that P2 neurons lose out in an activity-based competition for synaptic territory within the glomeruli and are not maintained at control numbers due to a lack of trophic support from the bulb.