Maturation and synapse formation of olfactory sensory neurons after injury

The olfactory system is a great model to ask questions related to neuronal regeneration, axon guidance and synapse formation. Processing of smell begins in the olfactory epithelium where sensory neurons are present and the olfactory bulb is the first stop in processing odor information in the central nervous system. While the olfactory bulb has neurons that regenerate as well, we are interested in the regeneration that occurs in the olfactory epithelium after being injured because it possesses a source of neural stem cells – something unique to the rest of the body. Earlier studies have proven that the introduction of methimazole will effectively damage the olfactory sensory neurons while keeping the neural stem cells intact. By using a fate mapping technique involving Cre-ERT2 mice, we are able to track the regeneration of these sensory neurons after a methimazole induced injury. Using immunohistochemistry in combination with ImageJ software analysis, we are able to pinpoint the colocalization of markers of new olfactory sensory neurons (green fluorescent protein (GFP)) with markers of neuron maturation (olfactory marker protein (OMP)) and synapse formation (tyrosine hydroxylase (TH) and synaptophysin). Analysis of maturation was done in the olfactory epithelium by studying the colocalization of the protein OMP and GFP. Data shows that after regeneration, neurons coexpress both markers 11 days after lesion. In the olfactory bulb, we characterized the recovery of synaptic markers TH and synaptophysin after axons reached the olfactory bulb, where olfactory sensory neuron axons make synaptic contacts with dendrites of projection neurons. Overall, these data are the first one to establish a timeline for axonal regeneration and synapse formation after injury in the olfactory system.