AGING, ATTENTION AND BENZODIAZEPINE RECEPTOR LIGANDS

本建议是一项竞争性续期申请。这个 建议的研究集中在年龄对调节的影响。 皮质胆碱能传入系统的活动和功能。这个 在前一个资助期进行的研究发现了新的 年龄对大脑皮层调节的影响 乙酰胆碱(ACh)释放和注意力能力。与之形成鲜明对比的是 年龄本身对皮质ACh释放的影响相当有限 注意功能，我们最近关于年龄对人的影响的实验 实验诱导的部分密度下降的动物 大脑皮层胆碱能输入。而去感觉化导致的 基础皮质ACh释放的减少在年轻人之间没有差别 和年老的动物，在刺激年轻的皮质ACh释放的同时- 去传入的动物与青年假去传入的动物是相同的 和老年/假去传入动物，老年/去传入动物展示 皮质ACh释放的增加强烈减弱了对 行为和神经药物刺激。这些数据表明，年龄 在去传入的动物中起到中介变量的作用，导致 胆碱能残留量的年龄相关性衰减 输入到大脑皮层以对刺激做出反应。拟议的研究 将测试关于神经机制的假设，这些机制介导了 衰老和部分去传入效应之间的交互作用 ACH版本，以及这种交互对 老年大鼠的注意能力。与年龄相关的认知障碍 可能源于年龄和先前存在的影响之间的相互作用 神经病理过程，以及皮质胆碱能下降 功能仍然是神经病理的主要候选对象 年龄相关认知障碍的发展，这项研究将 揭示了神经过程中的重要洞察力 年龄对受损皮质胆碱能神经元功能的影响 输入系统。

The present proposal represents a competitive renewal application. The proposed research focuses on the effects of age on the regulation of activity and functions of the cortical cholinergic afferent system. The research conducted during the previous funding period revealed new insights into the effects of age on the regulation of cortical acetylcholine (ACh) release and attentional abilities. In contrast to the rather limited effects of age per se on cortical ACh release and on attentional functions, our recent experiments on the effects of age in animals with an experimentally-induced partial decrease in the density of cortical cholinergic inputs. While the deafferentiation-induced decrease in baseline cortical ACh release did not differ between young and aged animals, and while stimulated cortical ACh release in young- deafferented animals was identical to that from young-sham-deafferented and aged/sham-deafferented animals, aged/deafferented animals exhibited a strongly attenuated increase in cortical ACh release in response to behavioral and neuropharmacological stimuli. These data suggest that age acted as an intervening variable in deafferented animals, resulting in an age-related attenuation of the capacity of residual cholinergic inputs to the cortex to respond to stimulation. The proposed research will test hypotheses about the neuronal mechanisms mediating the interactions between the effects of aging and partial deafferentation on ACh release, and about the significance of such interactions for the attentional abilities of aged rats. As age-related cognitive disorders may derive from interactions between the effects of age and pre-existing neuropathological processes, and as the decline in cortical cholinergic function remains a primary neuropathological candidate in the development of age-related cognitive disorders, this research will reveal important insights in the neuronal processes underlying the effects of age on the functions of a compromised cortical cholinergic input system.