Neurogenetic mechanisms underlying effects of chronic stress on vocal learning in adults and juveniles

慢性压力对成人和青少年声音学习影响的神经遗传机制

• 批准号: 10527057
• 负责人: TIMOTHY F WRIGHT
• 金额: $ 41.25万
• 依托单位: NEW MEXICO STATE UNIVERSITY LAS CRUCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10527057
• 关键词: Acculturation; Adolescent; Adult; Affect; Animal Model; Basal Ganglia; Behavior; Behavior Disorders; Behavioral; Binding; Biological Models; Birds; Brain; Brain region; Cell Nucleus; Cells; Child; Childhood; Chronic; Chronic stress; Cognition Disorders; Cognitive; Corpus striatum structure; Disease; Environment; Exposure to; FOXP1 gene; FOXP2 gene; Female; Foundations; Gene Expression; Genes; Genetic; Glucocorticoid Receptor; Glucocorticoids; Health; Hormones; Human; Immigrant; Individual; Knowledge; Language; Language Development; Learning; Life; Link; MAPK11 gene; Measures; Mediating; Melopsittacus; Memory; Modeling; Monitor; Nervous System Physiology; Neurons; Pathology; Pathway interactions; Personal Satisfaction; Phenotype; Physiological; Post-Traumatic Stress Disorders; Predisposition; Psittacidae; Social Interaction; Songbirds; Speech; Speed; Stress; Sum; Testing; Tissue-Specific Gene Expression; Traumatic Brain Injury; Women' s Group; Work; behavioral response; cognitive function; cognitive process; critical period; design; differential expression; early experience; early life stress; experience; experimental study; hypothalamic-pituitary-adrenal axis; learned behavior; life-long learning; male; neurogenetics; neuron development; novel; relating to nervous system; response; sex; social; social group; social integration; stress management; stressor; stroke recovery; stroke-induced aphasia; trait; transcriptome sequencing; vocal learning; vocalization; zebra finch

PROJECT SUMMARY Chronic stress can have diverse and often detrimental effects on cognitive function and overall health. When an individual is in a stressful situation, glucocorticoid (GC) hormones are released that bind to neurons and other cells expressing GC receptors, thereby altering gene expression and cellular activities. Although some changes driven by GC hormones can be beneficial in the short term, like mobilization of energy stores, repeated or chronic exposure to stressors can have many detrimental effects. Among these are a variety of behavioral and cognitive disorders, including diminished language learning. These effects have been well-studied in the context of early-life stress and vocal learning, in part through the use of avian model systems that are capable of learning early in life. How chronic stress experienced by adults affects their language learning is less understood, largely because of the lack of a suitable animal model. In this study we will employ a parrot model (the budgerigar, Melopsittacus undulatus) that, like humans, is capable of life-long learning to test the hypothesis that chronic stress reduces the ability of adults to learn new vocalizations via impacts on neuronal gene expression in the underlying neural centers of the brain. We will subject groups of adult budgerigars to either elevated or baseline chronic stress via environmental disruption and compare levels of circulating GC’s, speed and accuracy of vocal learning, and degree of social integration in the two treatments. We will also examine changes in the expression of GC receptors and key language-related genes in brain nuclei devoted to vocal learning. In a separate experiment, we will examine the interactions between early-life and adult chronic stress using a fully crossed experiment in which groups of budgerigars will experience either high or baseline stress as juveniles and again as adults (i.e. a double-hit model). We will then monitor the same behavioral and neural measures of vocal learning to test whether early life stress buffers individuals from the effects of stress during adulthood, or compounds the effects of later stress. In sum, these aims will comprehensively investigate the impacts of chronically elevated glucocorticoids on the cellular mechanisms mediating a key cognitive trait that underlies human speech and language.

项目概要 慢性压力会对认知功能和整体产生多种且通常有害的影响。 健康。当一个人处于压力状态时，会释放糖皮质激素（GC） 与表达 GC 受体的神经元和其他细胞结合，从而改变基因表达 和细胞活动。尽管 GC 激素驱动的一些变化可能有益于 短期内，例如能量储存的调动，反复或长期暴露于压力源可能会产生 许多有害的影响。其中包括各种行为和认知障碍， 包括语言学习的减少。这些影响已在以下背景下得到了充分研究： 早期生活压力和声音学习，部分是通过使用鸟类模型系统来实现的 能够在生命早期学习。成年人经历的慢性压力如何影响他们的语言 人们对学习的了解较少，很大程度上是因为缺乏合适的动物模型。在这项研究中 我们将采用鹦鹉模型（虎皮鹦鹉，Melopsittacus undulatus），它与人类一样， 能够终身学习来检验慢性压力会降低成年人能力的假设 通过影响底层神经元的神经元基因表达来学习新的发声 大脑的中枢。我们将对成年虎皮鹦鹉群体进行升高或基线测试 环境破坏造成的慢性压力，并比较循环 GC 的水平、速度和 两种治疗中声音学习的准确性和社会融合程度。我们还将 检查大脑中 GC 受体和关键语言相关基因表达的变化 致力于声乐学习的核心。在一个单独的实验中，我们将检查相互作用 使用完全交叉实验在早期生活和成年慢性压力之间进行研究，其中各组 虎皮鹦鹉在幼年时会经历高压力或基线压力，而成年后又会经历高压力或基线压力（即 双击模型）。然后我们将监测声音的相同行为和神经测量 学习测试早期生活压力是否可以缓冲个体免受压力影响 成年期，或加剧以后压力的影响。总之，这些目标将全面 研究长期升高的糖皮质激素对细胞机制的影响 调节人类言语和语言基础的关键认知特征。