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

项目摘要 慢性压力会对认知功能和整体健康产生各种各样的、往往是有害的影响。 健康当一个人处于紧张的情况下，糖皮质激素（GC）的激素释放 与神经元和其他表达GC受体的细胞结合，从而改变基因表达， 和细胞活动。虽然GC激素驱动的一些变化可能对 短期内，如动员能量储存，反复或长期暴露于压力源， 许多不利影响。其中包括各种行为和认知障碍， 包括语言学习能力下降。这些影响在以下背景下得到了充分研究： 早期生活压力和声音学习，部分通过使用鸟类模型系统， 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 对学习的了解较少，主要是因为缺乏合适的动物模型。本研究 我们将采用鹦鹉模型（虎皮鹦鹉，Melopsittacus undulatus），像人类一样， 能够终身学习，以检验慢性压力会降低成年人能力的假设 通过影响潜在神经元中的神经元基因表达来学习新的发声， 大脑的中心。我们将成年虎皮鹦鹉分为两组， 通过环境破坏的慢性压力，并比较循环GC的水平，速度和 发音学习的准确性，以及两种治疗中的社会融合程度。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 用于学习发声的细胞核。在另一个实验中，我们将研究 早期生活和成年慢性压力之间的关系，使用完全交叉实验，其中 虎皮鹦鹉将经历高或基线压力作为青少年和再次作为成年人（即 双重打击模式）。然后，我们将监测相同的行为和神经措施的声音 学习测试早期生活压力是否缓冲个人从压力的影响， 成年后，或复合后期压力的影响。总之，这些目标将全面 研究糖皮质激素长期升高对细胞机制的影响 介导了人类言语和语言的一个关键认知特征。

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.