QTL MAPPING OF COMPLEX LEARNING IN MICE

描述（改编自申请人摘要）： 人类的一般和特定认知功能部分由 遗传因素，但对介导这种变异的基因知之甚少。 复杂学习的遗传调控可以在动物模型中解决， 大脑结构的高度保守性语境与非语境 恐惧条件反射是一种复杂的情绪学习形式， 包括人类和啮齿动物。在情境恐惧条件反射中， 在一个特定的房间里，轻微的震动与声音的联系被显示为 恐惧反应直到最近，调控这种复合物的基因 表型很难定位，因为这是多基因的性质。 调控数量性状基因座（QTL）分析的最新应用， 连锁分析的形式，允许鉴定5个QTL， 1、2、3、10和16号染色体解释了70%的遗传变异 C57 BL/6（B6）和DBA/2（D2）之间的情境恐惧条件反射。一些 这些QTL与其他实验室中鉴定的调控 情绪性或情境恐惧条件反射在其他遗传交叉。因此，在本发明中， 这两个QTL都是在小鼠品系间通用的， B6和D2菌株之间的差异已经被确定。 所提出的研究的目标是缩小这些QTL区域，以便进一步研究。 study.该提案的具体目标是：1）。创造同类小鼠 染色体1和3上的QTL，调节背景恐惧 条件反射和非情境恐惧条件反射， B6和D2小鼠的杂交。2.）的情况。为了检验恐惧条件化的QTL是否 也调节其他形式的复杂学习中的遗传变异， 与恐惧有关的行为。3.）第三章为了表征基因表达的差异 在幼稚小鼠中，间隔特异性同源基因与B6背景菌株之间 以及情境恐惧条件反射后的情况 我们的长期目标是确定调控行为的基因， 希望应用这些信息来了解 人类学习的规律。对这种学习形式的研究不仅 适用于正常的复杂学习过程，也适用于某些 创伤后应激综合症之类的精神疾病

DESCRIPTION (Adapted from applicant's abstract): Individual differences in general and specific cognitive function in humans are regulated in part by genetic factors but little is known about the genes mediating this variation. Genetic regulation of complex learning can be addressed in animal models due to the highly conserved nature of brain structures. Contextual and noncontextual fear conditioning, a form of complex emotional learning, can be measured in both human and rodents. In contextual fear conditioning, learning the association of a mild shock with a sound in a particular chamber is shown as a fear response. Until recently, the genes regulating this type of complex phenotype have been difficult to map because of the polygenic nature of this regulation. The recent application of quantitative trait loci (QTL) analysis, a form of linkage analysis, allowed the identification of five QTLs on chromosomes 1, 2, 3, 10 and 16 that explain 70% of the genetic variation between C57BL/6 (B6) and DBA/2 (D2) for contextual fear conditioning. Some of these QTLs overlap with QTLs identified in other laboratories regulating emotionality or contextual fear conditioning in other genetic crosses. Thus, both QTLs that generalize across strains of mice and QTLs specific to the differences between B6 and D2 strains have been identified. The goal of the proposed studies is to narrow these QTL regions for further study. The specific aims of the proposal are: 1.) To create congenic mouse lines for QTLs on chromosomes 1 and 3 which regulate contextual fear conditioning and noncontextual fear conditioning identified previously in a cross of B6 and D2 mice. 2.) To examine whether the QTLs for fear conditioning also regulate genetic variation in other forms of complex learning or fear-related behaviors. 3.) To characterize differences in gene expression between interval-specific congenics and the B6 background strains in naive mice and after contextual fear conditioning. Our long-term goal is to identify the genes that regulate behavioral differences in mice with the hopes that applying this information to understand regulation of human learning. Studies of this form of learning are not only applicable to normal complex learning processes but also to certain psychopathologies like post-traumatic stress syndrome.