REGULATED GENETIC STUDIES OF MEMORY FORMATION

描述（改编自申请人的摘要）：记忆功能被认为是 神经元之间突触连接强度的变化 在学习过程中以适当的模式被激活。 目前的建议的目标是阐明钙/钙调素的作用 蛋白激酶II（CaMKII）在这种类型的活动依赖性突触 可塑性和记忆形成。 刺激CaMKII， 海马体，一个对人类和人类记忆形成都很重要的结构， 和实验动物，改变了神经元的能力， 活动依赖性突触可塑性：长时程增强（LTP）和 长期抑郁症（LTD） 一种新的遗传学方法将用于 表达激活的Ca 2+非依赖性突变CaMKII转基因， 解剖学和时间调节的方式，以测试几个 关于CaMKII在LTP和记忆储存中功能的假说。 目标1 CaMKII激活对所需刺激频率的影响 产生LTP或LTD将被确定，以及潜在的机制 任何变化都将被探索。 在目标2中，激活的假设 CaMKII通过改变突触可塑性和记忆来发挥其作用。 将测试钙调蛋白的可用性。 在目标3中，假设LTP在 5-10赫兹的频率范围是学习、记忆巩固所必需的 和/或记忆回忆将被测试。 最后，在目标4中， 将确定海马在介导学习和记忆缺陷中的作用。 这些实验将提供深入了解CaMKII和LTP的作用， 记忆的形成，这可能使药理学的发展， 用于治疗各种病理状况的干预措施， 影响记忆。

DESCRIPTION (Adapted from applicant's abstract): Memory function is thought to involve changes in the strength of synaptic connections between neurons that are activated in the appropriate patterns during the learning process. The goal of the current proposal is to elucidate the role of Ca2+/calmodulin protein kinase II (CaMKII) in this type of activity-dependent synaptic plasticity and in memory formation. Stimulation of CaMKII in the hippocampus, a structure important for memory formation in both human beings and experimental animals, alters the ability of neurons to undergo two forms of activity-dependent synaptic plasticity: long-term potentiation (LTP) and long-term depression (LTD). A novel genetic approach will be used to express an activated Ca2+-independent mutant CaMKII transgene in both an anatomically and temporally regulated manner in order to test several hypotheses regarding CaMKII function in LTP and memory storage. In Aim 1 the effect of CaMKII activation on the stimulation frequency required to produce either LTP or LTD will be determined, and the underlying mechanism of any change will be explored. In Aim 2 the hypothesis that activated CaMKII exerts its effect on synaptic plasticity and memory by altering calmodulin availability will be tested. In Aim 3 the hypothesis that LTP in the 5-10 Hz frequency range is required for learning, memory consolidation and/or memory recall will be tested. Finally, in Aim 4 the role of the hippocampus in mediating the learning and memory defects will be determined. These experiments will provide insight into the role of CaMKII and LTP in memory formation, which might allow the development of pharmacological interventions for the treatment of various pathological conditions which affect memory.