AGE RELATED LEARNING AND MEMORY IMPROVEMENTS

学习和记忆（L&M）的变化随着年龄的增长而发生，但对其潜在的分子和细胞原因知之甚少。小鼠表现出与年龄相关的食物偏好社会传递（STFP）和环境条件反射。值得注意的是，K+通道辅助亚基Kv β 1.1的穆尔突变改善了这些任务中的L&M，特别是在老年小鼠中。相比之下，这种突变要么削弱了年轻小鼠在这些任务中的表现，要么没有影响。与增加的缓慢后超极化（sAHP）有助于年龄相关的L&M缺陷的假设一致，老年Kv β 1.1突变体的sAHO与年轻野生型（WT）小鼠的sAHO相当，但显著小于老年WT。本提案的具体目的是：进一步表征老年Kv β 1.1-/-突变小鼠中L&M拯救的行为决定因素。确定Kv beta1.1.-/-引发的L&M改进的时间进程突变为了确定在Kv β 1.12.-/-中拯救依赖于多巴胺的L&M的电生理机制，变种人获得具有神经特异性和诱导性Kv β 1.1突变的小鼠。这里提出的研究不仅将进一步加深我们对kv β 1.1作用的理解。在年龄依赖性L&M，但他们也将是至关重要的发展战略，以克服这些L&M的障碍。此外，这些研究将进一步加深我们对sAHP、LTP和L&M之间可能联系的理解。

Changes in learning and memory (L&M) occur with aging, but little is known about their underlying molecular and cellular causes. Mice show age-related social transmission of food preference (STFP), and contextual conditioning. Remarkably, a mull mutation of the K+ channel auxiliary subunit Kvbeta1.1 improves L&M in these tasks, specifically in aged mice. In contrast, this mutation either impaired or had no effect in the performance of young mice in these tasks. Consistent with the hypothesis that an increased slow after-hyperpolarization (sAHP) contributes to age- related L&M deficits, the sAHO of the aged Kvbeta1.1 mutants is comparable to that of young wild type (WT) mice, but significantly smaller than aged Wts. The specific aims of this proposal are: To further characterize the behavioral determinants underlying the rescue of L&M in aged Kvbeta1.1-/- mutant mice. To determine the time course for the L&M improvements triggered by the Kvbeta1.1.-/- mutation. To identify the electrophysiological mechanisms underlying the rescue of hippocampal-dependent L&M in the Kvbeta1.12.-/- mutants. To derive mice with neural specific and inducible mutations of Kvbeta1.1. The studies proposed here will not only further our understanding of the role of kvbeta1.1. in age-dependent L&M, but they will also be crucial for developing strategies to overcome these L&M impairments. Additionally, these studies will further our understanding of the possible connections between sAHP, LTP and L&M.