AGE RELATED LEARNING AND MEMORY IMPROVEMENTS

学习和记忆的变化(L和M)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。老鼠表现出与年龄相关的食物偏好的社会传递(STFP)和背景条件作用。值得注意的是，K通道辅助亚单位Kvbeta1.1的MULL突变改善了L和M在这些任务中的表现，特别是在老年小鼠中。相比之下，这种突变要么损害了幼鼠在这些任务中的表现，要么没有影响。与慢后超极化增加导致年龄相关性L&M缺陷的假设一致，老年Kvbeta1.1突变体的SAHO与年轻野生型(WT)小鼠相当，但显著小于老年野生型(WT)小鼠。这项建议的具体目的是：进一步表征在老年Kvbeta1.1-/-突变小鼠中拯救L&M的行为决定因素。确定由Kvbeta1.1.-/-突变引发的L&M改善的时间进程。目的：探讨Kvbeta1.12.-/-突变体挽救海马依赖的L和M的电生理机制。获得神经特异的、可诱导的Kvbeta1.1突变小鼠。这里提出的研究不仅将加深我们对kvbeta1.1作用的理解。在依赖年龄的L&M中，他们也是至关重要的，但他们也将对制定策略以克服L&M的这些障碍至关重要。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.