P1: AGING & GENES IN LEARNING & LONG TERM POTENTIATION: ALZHEIMERS

阿尔茨海默病（AD）的特征是进行性衰退 学习和记忆等认知过程。 海马 参与学习和记忆，并在AD患者中受到影响。 学习和记忆也会随着正常的衰老而发生。 据信 学习和记忆过程可能是由突触介导的， 可塑性 这些研究的主要目的是调查 长时程增强的持续时间，突触可塑性的一种形式， 衰老受损动物及衰老对基因表达的影响 在学习依赖于营地的空间学习过程中， 长时程增强在体内自由活动的动物。 具体目标 I实验将描述年老、受损或衰老的动物的特征 在空间学习方面没有缺陷。 动物将用于永久性 内侧或外侧穿支通路中的电极植入-CA 3 突触来研究长时程增强的持续时间， 突触 在《特定目标2》中， 一些候选基因的时间和空间mRNA表达 和细胞色素氧化酶的活性。 在老年人中， 老年未受损动物，实验将比较mRNA表达 hzf-3、tPA、聚集蛋白和LAG的表达， 细胞色素氧化酶的活性。 在 具体目标3实验将研究hzf-3的mRNA表达， tPA、agrin和LAG与细胞色素氧化酶活性的关系 内侧和外侧穿支通路的长时程增强-CA 3 突触 拟议研究的研究结果 对老龄化研究的重要意义。 一个长期存在的概念， 学习和记忆的关键在于突触连接的改变 可能是学习和记忆过程的基础 如果在学习过程中发生突触修饰的永久性变化， 这些变化也必须反映在基因层面上。 因此如果 突触可塑性的降低和基因表达的减少， 在空间学习能力受损的老年动物中观察到表达， 那么这与年龄相关的学习障碍 基因表达可能揭示了 与衰老有关的认知障碍 此外，减少 in.细胞色素氧化酶在学习和突触可塑性中的活性 将表明这种酶在认知过程中很重要。

Alzheimer's disease (AD) is characterized by a progressive decline of cognitive processes such as learning and memory. The hippocampus is involved in learning and memory and is affected in AD patients. Learning and memory also occurs with normal aging. It is believed that learning and memory processes may be mediated by synaptic plasticity. The major goal of these studies is to investigate the duration of long-term potentiation, a form of synaptic plasticity in the aged impaired animals and the effect of aging on gene expression during learning of a hippocampal-dependent spatial learning and long-term potentiation in vivo freely moving animals. In Specific Aim I experiments will characterize animals that are aged impaired or aged unimpaired in spatial learning. Animals will be used for permanent electrode implantation in the medial or lateral perforant path-CA3 synapse to investigate the duration of long-term potentiation at these synapses. In Specific Aim 2 experiments will investigat e the temporal and spatial mRNA expression of a number of candidate genes and cytochrome oxidase activity during learning. In aged impaired and aged unimpaired animals, experiments will compare the mRNA expression of hzf-3, tPA, agrin, and LAG by using in situ hybridization, and the activity of cytochrome oxidase by using histochemical techniques. In Specific Aim 3 experiments will investigate mRNA expression of hzf-3, tPA , agrin and LAG and the activity of cytochrome oxidase activity in long-term potentiation in the medial and lateral perforant path-CA3 synapse. The research findings from the proposed studies have important implications to aging research. A long-standing notion in learning and memory is that modifications of synaptic connections within the nervous system may underlie learning and memory processes. If permanent changes in synaptic modifications occur during learning, these changes must also be reflected at the genetic level. Thus if both a decrease in synaptic plastic ity and a decrease in gene expression is observed in aged impaired in spatial learning animals, then this a relationship between aged related impairment in learning and gene expression may shed light into the mechanisms associated with cognitive impairment associated with aging. Further, a decrease in.'cytochrome oxidase activity in learning and synaptic plasticity will suggest that this enzyme is important in cognitive processes.