AGE RELATED MEMORY CHANGES IN KVB11 DEFICIENT MICE

这个项目的长期目标是阐明与年龄有关的学习和记忆缺陷的神经机制。 最近，我们的实验室已经创建了一种小鼠品系，其中钾通道的Kv β 1.1亚基已被删除。 Kv beta1.1亚基的缺失在年轻的Kv beta1.1突变体中产生了依赖于海马区的学习障碍。 值得注意的是，年龄（大于18个月）Kv β 1.1突变体没有表现出这种损害，也没有表现出年龄匹配的野生型小鼠中常见的与年龄相关的记忆缺陷。 该提案的具体目标是1.进一步表征这些小鼠的学习行为，使用良好建立的行为范例（即Morris水迷宫和巴甫洛夫恐惧条件反射）和2.研究老年Kv β 1.1突变体中缺乏与年龄相关的学习缺陷的神经机制。 具体而言，将进行电生理实验，以探索Kv β 1.1.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。 这项拟议的研究将作为提高我们对人类学习和记忆中与年龄相关的变化的理解的基础，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.