Neurobehavioral Relations in Senescent Hippocampus

衰老海马的神经行为关系

• 批准号: 6573052
• 负责人: CAROL A. BARNES
• 金额: $ 67.46万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6573052
• 关键词: Macaca mulatta; age difference; animal old age; brain mapping; cell senescence; central neural pathway /tract; electrophysiology; hippocampus; laboratory rat; magnetic resonance imaging; memory disorders; neural information processing; neural plasticity; neuropsychology

DESCRIPTION (provided by applicant): The objective of this research program is to understand the basis of memory impairments that result from normal aging. Over the past 19 years we have discovered links between spatial memory deficits and age-related changes in hippocampal connectivity and plasticity at the cellular and network levels. While empirical focus on the hippocampus is justified because of this structures critical role in memory, the extent to which changes in upstream cortico-hippocampal inputs contribute to these age-related behavioral deficits is unknown. The perirhinal cortex is at the highest level of the ventral visual processing stream. It carries polymodal sensory information to the hippocampus, is extensively reciprocally connected with it, and is critical for memory in its own right. Whether it transmits degraded information to the aged hippocampus, resulting in deficits in visual perception or stimulus associations is thus a major question addressed in the present grant. A complementary question is whether the breakdown during aging in the connectivity and plasticity mechanisms of hippocampal circuits leads to defective associative binding among neocortical areas, and hence less robust stabilization of episodic memories. Understanding how the bi-directional interactions between these structures are altered by the aging process, and how such failures in network communication may contribute to behavioral deficits, could provide insights into the neural mechanisms of memory at all ages. To begin the process of integrating the past two decades of rodent work towards an understanding of human aging, the scope of the project will be expanded to include young and aged monkeys in addition to rodents. The animals will be behaviorally tested on a battery of tasks that are adaptable to both species and known to be sensitive to lesions of the hippocampus and to the perirhinal cortex. In the monkeys, high resolution quantitative structural MRI and eventual microscopic stereological analysis will be used to begin to define structural changes associated with physiological changes and memory impairments in the aged non-human primate. Electrophysiological experiments will focus on ensemble recordings from hippocampus and perirhinal cortex of behaving young and old monkeys, and on synaptic connectivity and plasticity of the hippocampal - perirhinal cortex in young and old rats. The combination of ensemble recordings in the awake, behaving, aged non-human primate, and functional electrophysiological characterization of connections in behaviorally-screened young and old rats, should lead to insights into the respective involvement of hippocampal and neocortical association areas to age-associated memory deficits. This is a prerequisite for successful development of therapeutic or preventative treatments for cognitive decline in the elderly.

描述（由申请人提供）：本研究计划的目的是了解正常衰老导致的记忆障碍的基础。在过去的19年中，我们发现了空间记忆缺陷与在细胞和网络水平上海马连通性和可塑性的年龄相关变化之间的联系。尽管由于这种结构在记忆中的关键作用，因此对海马的经验关注是合理的，但上游皮层 - 海马输入的变化在多大程度上导致这些与年龄相关的行为缺陷的影响尚不清楚。周围的皮质处于腹侧视觉处理流的最高水平。它将多种感觉信息带到海马，与之相互互惠相连，对内存本身至关重要。因此，它是否将降级信息传递给老年海马，导致视觉感知或刺激关联的缺陷是当前授予中的一个主要问题。一个互补的问题是，海马电路的连通性和可塑性机理的衰老中的分解是否导致新皮层区域之间的缔合性有缺陷，从而减少了情节记忆的稳定稳定性。了解这些结构之间的双向相互作用如何因老化过程而改变，以及网络通信中的这种失败如何导致行为缺陷，可以为所有年龄段的记忆神经机制提供见解。为了开始将过去二十年的啮齿动物工作整合到对人类衰老的理解的过程中，该项目的范围将扩大到除啮齿动物外，还包括年轻和老年猴子。这些动物将在适应于物种的一系列任务上进行行为测试，并已知对海马病变敏感和对周围皮层敏感。在猴子中，高分辨率定量结构MRI和最终的微观立体分析将开始定义与老年非人类灵长类动物的生理变化和记忆障碍相关的结构变化。电生理实验将集中于行为年轻和老猴子的海马和周围皮层的整体记录，以及年龄较大大鼠的海马 - 阴部皮层的突触连通性和可塑性。在醒着，行为，年龄的非人类灵长类动物中的合奏记录的结合以及行为筛查的年轻大鼠和新老鼠的连接的功能性电生理表征，应深入了解海马和新皮层关联区域对年龄相关的记忆缺陷的各自参与。这是成功发展老年人认知能力下降的治疗或预防治疗方法的先决条件。