AGE RELATED MEMORY CHANGES IN KVB11 DEFICIENT MICE

该项目的长期目标是阐明与年龄相关的学习和记忆缺陷背后的神经元机制。最近，我们的实验室培育了一种缺失钾离子通道Kvbeta1.1亚基的小鼠。Kvbeta1.1亚基的缺失导致年轻的Kvbeta1.1突变体海马依赖性学习受损。值得注意的是，年龄较大（大于18个月）的Kvbeta1.1突变体没有表现出这种损伤，也没有表现出通常在年龄匹配的野生型小鼠中看到的与年龄相关的记忆缺陷。本建议的具体目的是：1。进一步表征这些小鼠的学习行为，使用已建立的行为范式（如莫里斯水迷宫和巴甫洛夫恐惧条件反射）的组合。研究老年Kvbeta1.1突变体中缺乏年龄相关学习缺陷的神经元机制。具体来说，我们将通过电生理实验来探讨Kvbeta1.1。突变体可能表现出神经元兴奋性的改变，以及这些改变如何影响被认为介导学习和记忆的特定形式的突触可塑性。这项研究将为我们进一步了解人类学习和记忆的年龄相关变化提供基础，从而有助于改善老年人的认知能力下降。

The long-term objective of this project is to elucidate the neuronal mechanisms that underlie age-related deficiencies in learning and memory. Recently, our laboratory has created a strain of mice in which the Kvbeta1.1 subunit of the potassium channel has been deleted. Deletion of the Kvbeta1.1 subunit produced impairments in hippocampus-dependent learning in young Kvbeta1.1 mutants. Remarkably, aged (greater than 18 mo.) Kvbeta1.1 mutants showed no such impairment and do not exhibit the age-related memory deficits normally seen in age-matched wild-type mice. The specific aims of this proposal are to 1. Further characterize the learning behavior of these mice, using a combination of well established behavioral paradigms (i.e. Morris water maze and Pavlovian fear conditioning) and 2. Investigate the neuronal mechanisms that underlie the absence of age-related learning deficits in the aged Kvbeta1.1 mutants. Specifically, electrophysiological experiments will be conducted to explore the possibility that the Kvbeta1.1. mutants might exhibit alterations in neuronal excitability and how these alterations might affect specific forms of synaptic plasticity thought to mediate learning and memory. The proposed research will serve as the basis for improving our understanding of age-related changes in human learning and memory and thereby help in the amelioration of cognitive decline in the elderly.