Translational Models of Memory and Cognitive Control (Component 5 of 8)

与精神疾病易感性相关的行为特征有显著的保守性。为 例如，人类的高特质新奇寻求是注意力缺陷/多动障碍的风险因素 和刺激物依赖，寻求新奇也是一种遗传特征，部分取决于类似的 其他物种的遗传机制。这个项目旨在将记忆的研究 机制和反应抑制。神经精神表型组学协会的组成部分， 将评估反应抑制或工作记忆的实验室测量的遗传性， 在一个非人类的既定谱系中寻求新奇和行为冲动的自然主义措施 适合于表现出显著的表型的数量性状连锁分析的动物 遗传性高密度SNP作图将集中在最强连锁的区域和靶区域 与人类的相似特征有关。在人群筛查之后， 表型，组将构成根据极端偏离正常的性状， 兴趣（例如，高新奇寻求/反应抑制差），这些组将使用 非侵入性的结构和分子成像，以评估的假设，具体修改， 多巴胺传递介导基因型-表型关系。 这个项目与正在进行的健康人和那些 与精神疾病，旨在揭示新的遗传机制，有助于人类 神经精神疾病相关的特征，表征这些特征的新的翻译模型， 对基因型之间的分子和细胞表型产生新的见解 和复杂的行为表型。

There is remarkable conservation of behavioral traits related to vulnerability for mental illness. For example, high trait novelty-seeking in humans is a risk factor for attention deficit/hyperactivity disorder and stimulant dependence, and novelty-seeking is also a heritable trait determined in part by similar genetic mechanisms in other species. This project, designed to bridge the studies of memory mechanisms and response inhibition.components in the Consortium for Neuropsychiatric Phenomics, will evaluate the heritability of a laboratory measures of response inhibition or working memory and naturalistic measures of novelty-seeking and behavioral impulsivity in an established pedigree of nonhuman animals suitable for quantitative trait linkage analyses of phenotypes exhibiting substantial heritability. High density SNP mapping will focus on regions of strongest linkage and on target regions discovered to associate with similar traits in humans. Subsequent to population-wide screening for phenotypes, groups will be constituted according to extreme deviation from normal on the traits of interest (e.g., high novelty-seeking/poor response inhibition), and these groups will be evaluated using non-invasive structural and molecular imaging to evaluate the hypothesis that specific modifications in dopamine transmission mediate the genotype-phenotype relationships. This project, which is tightly coupled to on-going behavioral genetic studies in healthy people and those with psychiatric disorders, is designed to uncover new genetic mechanisms contributing to human neuropsychiatric disease-related traits, characterize new translational models for these traits and generate new insights about the molecular and cellular phenotypes intermediate between genotypes and complex behavioral phenotypes.