GENETIC STUDIES: ROLE OF PROTEIN KINASE C IN LEARNING

我们实验室以前的研究表明，基因 空间学习成绩的差异可以用 莫里斯水务任务。C57BL/6小鼠表现相对较好 而DBA/2小鼠在这项任务中表现不佳。这些菌株和 用C57×DBA/2杂交组合产生的许多重组自交系 显示空间学习成绩的差异以及这种差异 与海马区蛋白激酶C显著相关 活动。蛋白激酶C(PKC)是通过产生 二酰甘油在磷脂酰肌醇周转过程中的重要作用 大脑中的第二信使。因为PKC在 大脑，它为进一步研究提供了重要的底物 使用遗传学方法进行调查。 我们的目的是研究海马区PKC在确定 不同性别学生学习成绩的遗传差异 透视。DBA小鼠学习缺陷的性质将 使用行为学方法进行进一步检查。这个问题是 蛋白激酶C活性是否随训练而变化 也将接受调查。 生化研究将被设计用来阐明 大鼠海马区PKC活性的品系差异 C57和DBA小鼠的同工酶图谱。分子遗传学 研究将检查主要的PKC基因的DNA序列 C57和DBA小鼠；这些基因在脑和脑中的表达 训练对基因表达的潜在影响；以及区域 这一表达的定位将通过原位检测进行 混血。 拟议研究的结果应该允许更完整的 评估空间学习成绩缺陷的性质， 并提供有关今后纠正的方法的信息 这样的赤字。此外，海马区PKC在脑组织中的作用 学习和记忆的过程应该被描绘出来。

Previous studies from our laboratory have indicated that genetic differences in spatial learning performance can be revealed using the Morris water task. C57BL/6 mice performed relatively well while DBA/2 mice perform poorly on the task. These strains and many recombinant inbred strains generated from a C57 X DBA/2 cross show variation in spatial learning performance and this variation is significantly correlated to hippocampal protein kinase C activity. Protein kinase C (PKC) is activated via generation of diacylglycerol during phosphatidyl inositol turnover, an important second messenger in brain. Because of the central role of PKC in the brain, it provides an important substrate for further investigation using a genetic approach. We purpose to examine the role of hippocampal PKC in determining genetic differences in learning performance from several perspectives. The nature of the learning deficit in DBA mice will be examined further using behavioral approaches. The question of whether protein kinase C activity changes as a function of training will also be investigated. Biochemical studies will be designed to elucidate the nature of the strain differences in hippocampal PKC activity by investigating the isozymic patterns in C57 and DBA mice. Molecular genetic studies will examine the DNA sequence of the major PKC genes from C57 and DBA mice; the expression of these genes in brain and potential effects of training on gene expression; and the regional localization of this expression will be examined by in situ hybridizations. The results of the proposed studies should allow a more complete assessment of the nature of spatial learning performance deficits, and provide information as to approaches for the future correction of such deficits. Furthermore, the role of hippocampal PKC in learning and memory processes should be delineated.