The regenerative capacity of the olfactory system makes it an attractive model to study neural circuit restoration after disruption. Our studies of olfactory development have demonstrated the close interaction that exists between plasticity, regeneration and sensory activity in the olfactory bulb (OB). We believe this interaction extends beyond development and into adulthood such that many of the same mechanisms are utilized during the formation, refinement and regeneration of olfactory circuitry. In addtion, these same mechanims may play a role in the olfactory response to neural damage or degeneration. To gain an understanding of these processes we established two distinct in vivo models of olfactory circuit disruption and repair each of which centers on the OB and can be used to study the underlying neural mechanisms. The first focuses on physical disruption with a mouse model for Traumatic Brain Injury. The second is based on pathological insult associated with neurodegenerative disease. Both models produce clear olfactory neural loss and circuit disruption with the potential for anatomical and functional restoration. These studies have revealed both common and unique aspects of olfactory disruption associated wih each model as well as differing capacities for restoration. Our data show that activation of a range of reactive and protective mechanims induced in the surrounding neural tissue following insult as well as various developmental programs. Current efforts center on increasing the restoration of olfactory circuitry by enhancing the developmantal mechanims. These studies will provide a unique understadning of olfactory regeneration as well as insight into potantial treatments for neural damage.
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