QTL MAPPING OF COMPLEX LEARNING IN MICE

在学习和记忆任务中的认知功能和表现 至少在一定程度上是由遗传因素引起的。中国的长期目标是 拟议的研究是使用基因实验策略来识别 是复杂学习和记忆过程的重要神经底物。 提供的数据表明，C57BL/6和DBA/2小鼠在 在许多复杂的学习任务上的表现被认为是 取决于海马体结构的完整性，包括 情境恐惧条件性冻结任务与空间版本的 莫里斯水务任务。C57BL/6和DBA/2小鼠在 简单的辨别任务表明 DBA/2菌株不是由于动机或注意力问题造成的。 经典遗传分析和重组近交系的结果 分析表明，这些菌株的复杂学习和记忆是 受多基因系统调控。 这里提出的研究旨在绘制染色体基因座图 调节C57BL/6和DBA/2小鼠复杂的学习记忆过程。 将使用数量性状基因座(QTL)分析方法进行 从研究中走出来。QTL是包含影响基因的染色体位点 在种群中表现出连续分布的特征。QTL 与背景恐惧相关的条件冻结将被分析 在BXD(C57BL/6 X DBA/2)中，重组近交系菌株和动物来自 C57BL/6×DBA/2杂交F_2代。育种研究将是 以检查任何有希望的QTL对行为的影响 在这个学习和记忆任务中的表现。 这些研究的结果应提供关于 人类学习和记忆的基因调控通过已知的 老鼠和人类基因组之间的同步性。

Cognitive function and performance on learning and memory tasks are mediated, at least in part, by genetic factors. The long-term goal of the proposed research is to use genetic experimental strategies to identify important neural substrates for complex learning and memory processes. Data are presented indicating that C57BL/6 and DBA/2 mice differ in performance on a number of complex learning tasks that are thought to be dependent on the integrity of the hippocampal-formation including a contextual fear-conditioned freezing task and the spatial version of the Morris water task. C57BL/6 and DBA/2 mice do not differ in performance on simple discrimination tasks suggesting that the behavioral impairment in the DBA/2 strain is not due to motivational or attentional problems. Results of classical genetic analyses and recombinant inbred strain analyses indicate that complex learning and memory in these Strains is regulated by polygenic systems. The studies proposed here are designed to map the chromosomal loci that regulate complex learning and memory processes in C57BL/6 and DBA/2 mice. The quantitative trait loci (QTL) method of analysis will be used to carry out the research. QTLs are chromosomal loci that contain genes influencing traits that exhibit continuous distributions in a population. QTLs that are associated with contextual fear-conditioned freezing will be analyzed in BXD (C57BL/6 X DBA/2) recombinant inbreds strains and animals from the F2 generation of a C57BL/6 X DBA/2 cross. Breeding studies will be conducted to examine the impact of any promising QTLs on behavioral performance in this learning and memory task. The results of these studies should provide important information on genetic regulation of learning and memory in humans by virtue of the known synteny between the mouse and human genomes.