In previous studies we determined that OSN projections to the OB could restore their proper order following broad axonal disruption (Cheng et al., 2011). This extraordinary capacity to rewire itself has enabled us to establish the olfactory system as a model for studying neural repair associated with disease related neurodegeneration or traumatic brain injury (TBI). Since Olfactory dysfunction is an early indicator of many neurological disorders including Alzheimer disease and Parkinsons disease we hypothesized the olfactory system may be ultrasensitive to disease related factors and thus would offer better insight to early stages of these disorders. Thus we established an in vivo mouse model that indeed produces visible neuronal cell death by 3 weeks of age simply by expressing a mutant Amyloid Precursor Protein (APP) in OSNs (Cheng et al. 2011). Recently we determined that the resulting neurodegeneration has downstream affects on the OB circuitry that can be measured through anatomical, physiological and behavioral methods and are reversible when APP overexpression is eliminated (Cheng et al., 2012). Through our collaborative efforts with the Koretsky Lab at NINDS we have also been able to follow these anatomical changes using Manganese Enhanced MRI (MEMRI) suggesting that tracking neurodegeneration and repair may be possible through non-invasive scanning methods. Similarly, we have established an olfactory-based model to study TBI since loss of olfactory function is also commonly associated with head trauma. In doing so, we have introduced an olfactory bulb impact (OBI) model that demonstrates many of the same molecular and cellular characteristics as the controlled cortical impact (CCI) model but offers some unique advantages in that many cell types in the olfactory bulb can regenerate. Interestingly the olfactory phenotypes associated with each of these models are quite different at both the electrophysiological and behavior level. We are now determining the neuronal basis of these distinct olfactory changes as they could provide important phenotypic information to better localize the damage associated with TBI.
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