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

基本信息

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
项目类别：
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&apos 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

项目摘要

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.

项目摘要慢性压力会对认知功能和整体产生潜水员和经常有害的影响健康。当一个人处于压力状态时，糖皮质激素（GC）激素会释放与表达GC受体的神经元和其他细胞结合，从而改变了基因表达和细胞活动。尽管GC激素驱动的一些变化可能对短期，例如动员能量存储，重复或长期暴露于压力源许多有害影响。其中包括各种行为和认知障碍，包括语言学习减少。这些影响在早期生活压力和声音学习，部分是通过使用禽模型系统能够在生命的早期学习。成年人经历的慢性压力如何影响他们的语言学习的理解程度不高，主要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（Budgerigar，Melopsittacus undulatus），就像人类一样能够终身学习能够检验慢性压力降低成人能力的假设通过对基础神经元中神经元基因表达的影响学习新的发声大脑中心。我们将使成人Buckegars组成升高或基线通过环境中断和比较循环GC的水平，速度和声音学习的准确性和两种治疗中的社会融合程度。我们也会检查大脑中GC受体和关键语言基因表达的变化致力于声带学习的核。在另一个实验中，我们将检查相互作用在早期生活和成人慢性压力之间使用完全交叉的实验，其中的组 Budgerigars将以少年的身份经历高或基线应力，并再次作为成年人（即双重打击模型）。然后，我们将监视声音的相同行为和神经测量学会测试早期生活压力是否使个人是否从压力的影响中缓冲成年或使后来的压力的影响更加复杂。总而言之，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介导人类言语和语言的基础的关键认知特征。