Non-uniform endogenous regeneration of olfactory sensory neuron axons across the mouse olfactory bulb.

Olfactory sensory neurons (OSNs) are generated throughout life and can be repopulated even after complete ablation. However, the extent to which OSN axonal input to the olfactory bulb (OB) recovers after OSN ablation is unclear, with some studies reporting complete regeneration of specific glomeruli, while others find regeneration deficits, and most studies focusing on anatomical measures of recovery. Here, we identified profound deficits in the recovery of odor-evoked responses in OSN axons in the dorsal OB five weeks after OSN ablation, a time point at which OSNs have repopulated the OE. Histological analysis of mature OSN axons throughout the OB showed persistent deficits in re-formation of glomeruli in the dorsal and medial glomerular layer and in mature OSN axon filling of glomeruli in the dorsomedial OB. In contrast, the size, density and axon filling of glomeruli in the lateral and ventral regions of the OB were similar to those in control mice by 10 weeks after OSN ablation. This non-uniform axonal regeneration in an endogenously generated population of neurons provides a foundation to understand the mechanisms and factors necessary for successful circuit integration of stem cell-derived neurons.