GENETIC STUDIES--ROLE OF PROTEIN KINASE C IN LEARNING

我们实验室以前的研究表明， 空间学习表现的差异可以通过使用 莫里斯水任务 C57BL/6小鼠表现相对较好 而DBA/2小鼠在任务中表现不佳。 这些菌株和 C57 × DBA/2杂交产生的许多重组近交系 显示了空间学习性能的变化，这种变化 与海马蛋白激酶C显著相关 活动 蛋白激酶C（PKC）通过产生 磷脂酰肌醇周转过程中，一个重要的 大脑中的第二信使 由于PKC在 大脑，它提供了一个重要的基板， 使用遗传学方法进行研究。 我们的目的是研究海马PKC在决定 遗传差异的学习表现，从几个 视角 DBA小鼠学习缺陷的性质将 用行为学的方法进一步研究。 问题 蛋白激酶C活性是否随着训练而变化 也将被调查。 生物化学研究旨在阐明 海马PKC活性的品系差异 C57和DBA小鼠的同工酶谱。 分子遗传 研究将检查主要PKC基因的DNA序列， C57和DBA小鼠;这些基因在脑中的表达， 训练对基因表达的潜在影响; 这种表达的定位将通过原位杂交检测。 杂交 拟议研究的结果应能更全面地 评估空间学习表现缺陷的性质， 并提供有关今后纠正方法的信息 这样的赤字。 此外，海马PKC的作用， 学习和记忆过程应该被描述。

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.