AGING & GENES IN LEARNING & LONG TERM POTENTIATION: ALZHEIMERS

阿尔茨海默病(AD)的特征是进行性下降 认知过程，如学习和记忆。海马体 参与学习和记忆，并在AD患者中受到影响。 学习和记忆在正常衰老的情况下也会发生。据信， 学习和记忆过程可能是由突触介导的 可塑性。这些研究的主要目标是调查 长时程增强，突触可塑性的一种形式 衰老损伤动物及衰老对基因表达的影响 在海马区依赖的空间学习和学习过程中 在活体自由活动动物体内的长期增强作用。以特定的目标 I实验将描述衰老、受损或衰老的动物的特征。 在空间学习方面没有受到损害。动物将被用来永久 电极植入内侧或外侧穿支路径-CA3 Synapse研究这些脑区长时程增强的持续时间 突触。在特定的目标中，将进行2个实验来研究 多个候选基因的时空表达 以及学习过程中细胞色素氧化酶的活性。在老年人和弱智人士中 老化的未受损动物，实验将比较mRNA的表达 Hzf-3、tPA、agrin和LAG的原位杂交，以及 用组织化学方法检测细胞色素氧化酶活性。在……里面 特定目的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、外侧穿支通路CA3的长时程增强 Synapse。建议研究的研究结果包括 对衰老研究的重要启示。一种由来已久的观念 学习和记忆是突触连接的修改 神经系统内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改的永久性变化， 这些变化也必须在基因层面上反映出来。因此，如果 突触可塑性的降低和基因的减少 在空间学习动物中观察到老年受损的表达， 那么这是与年龄相关的学习障碍之间的关系 而基因表达可能有助于揭示与 与衰老相关的认知障碍。此外，减少了 学习和突触可塑性中的细胞色素氧化酶活性 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.