PLASTICITY IN THE STRESS AXIS

这项建议的重点是研究边缘-下丘脑- 垂体-肾上腺（LHPA）轴的变化作为一个功能的发展 事件，遗传易感性和暴露于反复的压力，以及如何 这些因素造成了压力的个体差异 在整个生命过程中，包括在衰老过程中。 压力暴露的确切时间和方式可能会导致 对内分泌、分子、神经元和 动物的行为功能。 理解“可塑性” 在帮助我们描述系统如何 保持对压力的最佳反应，以及它如何将过去的 体验到应对过程。 因此，我们将探讨这些问题 通过3组相互关联的研究：1）在一系列发展中， 研究中，我们将研究应激的神经基础 低反应期（SHRP）及其相关机制 随着动物的出现进入应激反应。 我们 我将研究4种早期压力模型的后果（母亲 剥夺不同的时间，和变化的窝仔数）的 SHRP的持续时间，以及成年后的应激反应， 专注于将大脑回路的变化与 内分泌概况和学习，记忆和对新奇事物的反应; 2） 在对衰老的研究中，我们将研究一些决定因素， 老年动物应激反应的个体差异 为了理解为什么有些动物受损，而另一些则没有， 他们会变老 我们将研究遗传易感性对 通过对比两个品系的大鼠，费舍尔和刘易斯， 已知其具有不同的应激反应曲线。 我们将 还研究在发展过程中发生的事件如何影响 老化过程，通过研究发展模型的后果， 随着动物年龄的增长，包括对应激反应的影响， 反应能力和学习记忆; 3）在针对年轻人的研究中， 成年动物，我们将研究的神经机制， 对反复的压力源敏感化和习惯化。 我们尤其 应关注特定大脑结构的作用（例如，的 视交叉上核和前额叶皮层）， 这种可塑性。 最后，我们将开始研究 NMDA受体在这些塑料过程中的潜在作用。 这 结合研究，我们应该更好地了解 在动物的整个生命过程中，应力轴是如何改变的，以及 这如何导致压力反应的个体差异 和应对

The focus of this proposal is to study how the limbic-hypothalamo- pituitary-adrenal (LHPA) axis changes as a function of developmental events, genetic predisposition and exposure to repeated stress, and how these factors contribute to individual differences in stress responsiveness throughout life, including during the aging process. Exactly when and how the stress exposure takes place may lead to different consequences on the endocrine, molecular, neuronal and behavioral functioning of the animal. Understanding the "plasticity" of the LHPA axis is important in helping us describe how the system maintains optimal responsiveness to stress, and how it incorporates past experience into the coping process. Thus we shall explore these issues via 3 interrelated sets of studies: 1) In a series of developmental studies, we shall examine the neuronal bases of the stress hyporesponsive period (SHRP) in the rat and the mechanisms associated with the animal's emergence from it into stress responsiveness. We shall look at the consequences of 4 models of early stress (maternal deprivation with various timing, and changes in litter size) on the duration of the SHRP, and on stress responsiveness in adult life, focusing on relating changes in the brain circuits to alterations in endocrine profiles and in learning, memory and response to novelty; 2) In studies focused on aging, we shall examine some of the determinants of individual differences in stress responsiveness in aged animals in order to understand why some animals are impaired and others are not as they age. We shall study the effect of genetic predisposition on the aging process by contrasting two strains of rats, Fisher and Lewis, which are known to have different stress response profiles. We shall also study how events taking place during development may impact on the aging process, by studying the consequences of the developmental models as the animals age, including effects on stress responsiveness, brain responsiveness and learning and memory; 3) In studies focused on young adult animals, we shall investigate the neuronal mechanisms of sensitization and habituation to repeated stressors. In particular, we shall focus on the role of specific brain structures (e.g., the suprachiasmatic nucleus, and the prefrontal cortex) in contributing to this type of plasticity. Finally, we shall begin to investigate the potential role of NMDA receptors in these plastic processes. This combination of studies should provide us with a better understanding of how the stress axis is modified throughout the life of the animal, and how this contributes to individual differences in stress responsiveness and coping.