Effects of cholinergic axonal plasticity on spatial orientation

项目总结/文摘

Project Summary/Abstract Neurodegenerative disorders can produce significant impairments in a patient’s ability to maintain spatial orientation. The current changing age structure of the US population in combination with lack of effective treatments for neurodegenerative disorders presents serious challenges for society in the management of these patients. Evaluating novel therapies for neurodegenerative disorders will depend on identifying an appropriate animal model of spatial orientation. Rats, like humans, use environmental and self-movement cues to maintain spatial orientation. My research has focused on developing tasks for rats that dissociate the use of either source of information. The basal forebrain cholinergic projections undergoes significant degeneration during the progression of Dementia of the Alzheimer's Type. The experiments outlined in this proposal represent the next step in investigating the potential of enhancing neuroplasticity to improve cognitive deficits associated with pathology in the basal forebrain cholinergic neurons. One goal of the proposal examines whether anti-Nogo-A immunotherapy is sufficient to promote neuroplasticity basal forebrain cholinergic neurons in adult and senescent rats. Another goal is to evaluate the extent that enhanced neuroplasticity at either age is sufficient to ameliorate self-movement cue processing deficits. A final goal is to provide training experiences for undergrad and graduate students that will establish a foundation to pursue a career in the biomedical sciences. The results of these studies will advance our understanding of the effects of aging on spatial orientation and evaluate the potential of anti-Nogo-A immunotherapies as a novel intervention for neurodegenerative disorders.