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，人类对新奇特质的高度追求是注意力缺陷/多动障碍的风险因素 和刺激性依赖，追求新奇也是一种可遗传的特征，部分由类似的 其他物种的遗传机制。这个项目旨在搭建记忆研究的桥梁 神经精神病学表型组学联合会中的机制和反应抑制， 将评估实验室反应抑制或工作记忆测量的遗传力 在一个已建立的非人类家系中对新奇探索和行为冲动的自然主义测量 适于对表现出实质性表型的数量性状连锁分析的动物 遗传力。高密度SNP作图将侧重于最强连锁的区域和目标区域 被发现与人类的相似特征有关。在进行全人群筛查之后 表型、类群将根据与正常性状的极差来组成 兴趣(例如，高度追求新颖性/反应抑制差)，这些群体将使用 非侵入性结构和分子成像评估特定修饰在 多巴胺传递介导了基因-表型关系。 该项目与正在进行的健康人行为遗传学研究密切相关 精神障碍，旨在揭示新的遗传机制有助于人类 神经精神疾病相关特征，表征这些特征的新翻译模型 对介于两种基因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.