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

记忆和认知控制的转化模型（第 5 部分，共 8 部分）

基本信息

批准号：
7675792
负责人：
J. DAVID JENTSCH
金额：
$ 6.96万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-30 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7675792
关键词：
15 year old Adult Aggressive behavior Animal Model Animals Anxiety Architecture Attention deficit hyperactivity disorder Basal Ganglia Behavioral Behavioral Genetics Binding Biological Birth Brain Brain region Categories Cercopithecus tantalus Cognitive Collaborations Complex Coupled Data Data Collection Data Set Databases Dependence Diagnostic Discipline Disease Dopamine Exhibits Face Finland Genetic Genetic Determinism Genome Genomic Segment Genomics Genotype Goals Heritability Human Human Resources Image Impulsivity Invasive Laboratories Life Link Macaca mulatta Maps Measures Mediating Memory Mental disorders Methods Modeling Modification Molecular Monkeys N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide Neurobiology Performance Phenotype Physiological Physiological Processes Population Predisposition Process Psychostimulant dependence Quantitative Trait Loci Range Research Resources Reversal Learning Risk Factors Sampling Screening procedure Short-Term Memory Single Nucleotide Polymorphism Map Stratification Temperament Testing Translational Research Universities Ursidae Family Variant cognitive control cognitive function cohort density design disease phenotype endophenotype forest forging frontal lobe gene discovery genetic linkage analysis genetic pedigree indexing insight interest male member molecular imaging neurochemistry neuromechanism neuropsychiatry nonhuman primate receptor receptor binding receptor function relating to nervous system response social trait transmission process vervet

项目摘要

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.

与精神疾病脆弱性有关的行为特征有明显的保护。为了例如，人类的高性状新颖性寻求新奇是注意力缺陷/多动症的危险因素和刺激性依赖和寻求新颖性也是一种可遗传的特征其他物种的遗传机制。该项目旨在弥合记忆的研究机制和反应抑制。将评估实验室响应抑制或工作记忆的遗传力以及自然主义的寻求新颖性和行为冲动的衡量指标适用于表现出色的表型定量性状连锁分析的动物遗传力。高密度SNP映射将集中在最强链接和目标区域上被发现与人类的类似特征相关联。在整个人口筛查之后表型，组将根据与正常的极偏差构成兴趣（例如，高新颖性/新颖性的抑制作用较差），将使用这些群体进行评估非侵入性结构和分子成像，以评估以下假设多巴胺传播介导基因型 - 表型关系。这个项目与健康人的持续行为遗传研究紧密结合使用精神病障碍，旨在发现有助于人类的新遗传机制神经精神疾病相关的特征，描述了这些特征的新翻译模型和产生有关基因型之间中间分子和细胞表型的新见解和复杂的行为表型。