EAGER: Linking lynx gene variations to inter-individual differences in cognitive function

EAGER：将山猫基因变异与认知功能的个体差异联系起来

• 批准号: 1745823
• 负责人: Julie Miwa
• 金额: $ 30万
• 依托单位: Lehigh University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2022-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1745823&HistoricalAwards=false
• 关键词: EAGER; Linking; lynx; gene; variations

Individuals differ greatly in their cognitive and creative abilities. Naturally occurring genetic variations are assumed to account for a significant proportion of these differences. The investigators will assess how naturally occurring variations in one gene family, the lynx genes, relate to cognitive and emotional functions in humans. Lynx gene variations alter brain function and cognitive and emotional behavior in mice model; this exploratory project addresses the link between lynx gene and behavior in humans. Results could inform the development of new therapeutic approaches for the treatment of cognitive impairments, such as those associated with Alzheimer's Disease, or observed after brain injury. The project could furthermore uncover the role of genetic factors for creative and artistic abilities and anxiety disorders. This in turn could help destigmatize mental disorders by providing a neurobiological basis for them and undergraduate students will be involved in every step of the scientific research process. The researchers are committed to increasing the representation of women and underrepresented minorities in STEM fields and will coordinate recruitment activities accordingly. Candidate genes have been identified in mouse models that regulate neuronal plasticity and influence cognitive and emotional behavior. This project aims to test how naturally occurring variations in these genes, lynx1 and lynx2, relate to inter-individual differences in cognitive and emotional functions in humans. A large number of individuals will be screened for single nucleotide polymorphisms (SNPs) and tested on a variety of cognitive and control measures in order to develop unique cognitive profiles of individuals harboring mutations in these genes. Predicted differences in fear learning and memory updating will be tested by comparing performance of individuals with and without SNPs in aversive conditioning and memory updating paradigms. The project is the first one to assess how lynx gene variations relate to cognitive and emotional functions in humans, and is therefore exploratory, but has the potential to uncover important biological pathways impinging on complex human cognition.

个体的认知和创造能力存在很大差异。自然发生的遗传变异被认为是这些差异的很大一部分原因。研究人员将评估山猫基因这一基因家族中自然发生的变异与人类认知和情感功能的关系。 Lynx基因变异改变小鼠模型的大脑功能以及认知和情绪行为；这个探索性项目探讨了山猫基因与人类行为之间的联系。结果可以为治疗认知障碍（例如与阿尔茨海默病相关的认知障碍或脑损伤后观察到的认知障碍）的新治疗方法的开发提供信息。该项目还可以揭示遗传因素对创造力和艺术能力以及焦虑症的作用。这反过来又可以通过为精神障碍提供神经生物学基础来帮助消除精神障碍的污名，并且本科生将参与科学研究过程的每一步。研究人员致力于增加女性和代表性不足的少数群体在 STEM 领域的代表性，并将相应地协调招聘活动。已在小鼠模型中鉴定出调节神经元可塑性并影响认知和情绪行为的候选基因。该项目旨在测试这些基因 lynx1 和 lynx2 中自然发生的变异如何与人类认知和情感功能的个体差异相关。将对大量个体进行单核苷酸多态性 (SNP) 筛查，并进行各种认知和控制措施测试，以便开发携带这些基因突变的个体的独特认知特征。通过比较具有和不具有 SNP 的个体在厌恶条件反射和记忆更新范式中的表现，可以测试恐惧学习和记忆更新的预测差异。该项目是第一个评估山猫基因变异如何与人类认知和情感功能相关的项目，因此具有探索性，但有可能揭示影响复杂人类认知的重要生物途径。