AGING, ATTENTION AND BENZODIAZEPINE RECEPTOR LIGANDS

目前的建议是一个竞争性的续期申请。的 建议的研究重点是年龄对调节的影响， 皮质胆碱能传入系统的活性和功能。的 在上一个资助期间进行的研究显示， 年龄对大脑皮层神经元调节的影响 乙酰胆碱（ACh）的释放和注意力。相比 年龄本身对皮质ACh释放的影响相当有限， 注意力功能，我们最近的实验对年龄的影响， 实验诱导密度部分降低的动物 皮质胆碱能输入的信号而传入神经阻滞引起的 基线皮质ACh释放的减少在年轻人之间没有差异， 和老年动物，而刺激皮质ACh释放在年轻的- 去传入动物与假去传入动物相同 和老年/假去传入动物，老年/去传入动物表现出 皮质ACh释放的强烈衰减增加， 行为和神经药理学刺激。这些数据表明，年龄 作为一个干预变量在deafferented动物，导致 与年龄相关的残留胆碱能神经元的能力衰减 输入到皮层对刺激做出反应。拟议研究 将测试有关神经元机制介导的假设， 衰老和部分传入神经阻滞对 乙酰胆碱释放，以及这种相互作用的意义， 老年大鼠的注意力。与年龄有关的认知障碍 可能来自年龄和预先存在的影响之间的相互作用 神经病理过程，并作为皮质胆碱能神经元的下降， 功能仍然是一个主要的神经病理学候选人， 与年龄相关的认知障碍的发展，这项研究将 揭示了神经元过程的重要见解， 年龄对受损皮质胆碱能神经功能的影响 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.