Effects of cholinergic axonal plasticity on spatial orientation

项目摘要/摘要 神经退行性疾病可导致患者维持空间的能力显著受损 定位。当前美国人口年龄结构的变化与缺乏有效的 神经退行性疾病的治疗给社会带来了严重的挑战 这些病人。评估神经退行性疾病的新疗法将取决于确定 适宜的动物空间定位模型。老鼠和人类一样，使用环境和自我运动的线索 以保持空间方向。我的研究重点是为大鼠开发任务，使其与使用 任何一种信息来源。基底前脑胆碱能投射显著变性 在阿尔茨海默氏型痴呆症的进展过程中。这项提案中概述的实验 代表下一步研究增强神经可塑性以改善认知缺陷的潜力 与病理有关的基底前脑胆碱能神经元。提案的一个目标是审查 抗Nogo-A免疫治疗是否足以促进基底前脑胆碱能神经可塑性 成年和衰老大鼠的神经元。另一个目标是评估增强的神经可塑性在多大程度上 无论哪种年龄，都足以改善自我运动线索加工缺陷。最终目标是提供培训 为本科生和研究生提供的经验，这些经验将为在 生物医学科学。这些研究的结果将促进我们对衰老影响的理解 抗Nogo-A免疫疗法作为一种新的干预措施的空间定位和评估 神经退行性疾病。

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.