QTL MAPPING OF COMPLEX LEARNING IN MICE

认知功能和学习记忆任务的表现是 至少部分由遗传因素介导。的长期目标 建议的研究是使用遗传实验策略来识别 复杂的学习和记忆过程的重要神经基质。 提供的数据表明C57 BL/6和DBA/2小鼠在以下方面不同： 在一些复杂的学习任务上的表现被认为是 取决于完整的露营形成，包括一个 背景恐惧条件冻结任务和空间版本的 莫里斯水任务。C57 BL/6和DBA/2小鼠在以下方面的表现没有差异 简单的辨别任务表明， DBA/2紧张不是由于动机或注意力问题。 经典遗传分析和重组近交系的结果 分析表明，这些菌株中复杂的学习和记忆能力， 由多基因系统调控。 这里提出的研究旨在绘制染色体基因座， 调节C57 BL/6和DBA/2小鼠复杂的学习和记忆过程。 数量性状基因座（QTL）分析方法将用于进行 出研究。QTL是染色体上的基因位点， 在群体中表现出连续分布的性状。QTL， 与情境性恐惧条件性冻结有关 在BXD（C57 BL/6 X DBA/2）重组近交系和来自 C57 BL/6 X DBA/2杂交的F2代。育种研究将是 研究任何有希望的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以下方面的重要信息： 人类学习和记忆的遗传调节， 小鼠和人类基因组的共线性。

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.