Genetic Dissection of a Motor Central Pattern Generator

中枢模式发生器（CPG）是一种节律性活跃的神经网络，是许多刻板印象的基础。 和重复的随意肌肉运动，如搅拌或液体舔。啮齿类动物的液体舔是一种 一个有前途的简单的CPG模型的例子：这是一种高度刻板的行为，其特征是 有节奏的舌头和下巴运动，它被认为是由分布在大脑中的神经基质控制的。 脑干中的网状结构在初步观察中，我们已经证明， 小鼠是研究舔CPG遗传基础的绝佳物种选择-常见的近交系 菌株C57 BL/6 J（B6）和DBA/2 J（D2）在舔率方面具有稳健的、非重叠的表型差异。 对舔食率差异基因的识别应该对研究 CPG。然后可以用基因靶向缺失或插入来创建小鼠，从而允许特定的生理或生理功能。 解剖学研究我们建议利用一种新增加的遗传资源， 舔体解剖：BXD高级重组近交（RI）菌株组。这些老鼠可以让 精确的遗传作图的数量性状基因座（QTL）的基础行为特征。我们建议使用 一种新的舔率高通量测定法，用于测试一组约80个BXD R1菌株，并绘制数量性状基因座 （QTL）具有高精度，其是舔率的品系变异的基础。 相关性：复杂的动物，如人类，拥有许多刻板的运动反应。 和/或重复性。刻板重复的基因和机制的比较 运动与塑性行为将成为许多人类CMS相关的信息来源 包括不正常的重复运动的疾病。

Central pattern generators (CPGs) are rhythmically active neural networks that underlie many stereotyped and repetitive voluntary muscle movements such as whisking or fluid licking. Fluid licking in rodents is an example of a promising, simple model of a CPG: It is a highly stereotyped behavior characterized by rhythmic tongue and jaw movements, and it is thought to be controlled by a neural substrate distributed in the medullary reticular formation in the brainstem. In preliminary observations, we have demonstrated that mice are a superb species choice for investigating the genetic basis of the licking CPG- the common inbred strains C57BL/6J (B6) and DBA/2J (D2) have a robust, non-overlapping phenotypic difference in lick rate. The identification of genes underlying differences in lick rate should have a huge payout for the study of CPGs. Mice can then created with gene-targeted deletions or insertions, allowing for specific physiological or anatomical investigation. We propose to take advantage of a newly augmented resource for our genetic dissection of licking: The BXD advanced recombinant inbred (Rl) strain set. These mice will allow for precision genetic mapping of quantitative trait loci (QTL) that underlie behavioral traits. We propose to use a novel high-throughput assay for lick rate to test a set of -80 BXD Rl strains, and map quantitative trait loci (QTLs) with high precision that underlie strain variation in lick rate. Relevance: Complex animals such as humans possess a number of motor responses that are stereotypic and/or repetitive in nature. Comparison of the genes and mechanisms underlying stereotyped repetitive movements vs. plastic behaviors will be a source of information relevant for a number of human CMS disorders involving abnormal repetitive movements.