EARLY EXPERIENCE ALTERS ADULT BEHAVIOR AND THE HPA AXIS

经济困难和药物滥用等情况往往对 养育孩子的方式严重影响了孩子的成长， 年轻人的发展。流行病学研究结果显示， 大约有一半的受虐儿童表现出神经损伤。 此外，这些饲养条件也是导致 随后的病理学和心理生理学。 目前，人们对 改变儿童养育方式的神经生物学后果， 一般来说，早期经验的变化。本文中描述的研究 应用程序旨在检查各种形式的早期 神经系统的发展经验，有助于动物的 应对晚年生活中的压力。我们认为这是一个重要的 终点，因为成功适应压力刺激的能力 对有机体的健康至关重要;也许对现代人来说， 工业化社会。我们将集中研究中央 促肾上腺皮质激素释放因子（CRF）系统，因为许多研究 暗示这些回路是协调内分泌的重要介质， 自主神经系统和对压力的行为反应。通用报告格式- 下丘脑致密的室旁核， CRF终末野起源于正中神经血管区 隆起和来源的一些传出植物中心在 脑干，是理想的位置，以协调不同的调整， 是在急性或慢性压力下生存所必需的。的最新证据 我们的实验室表明，发展至少一些中央CRF， 电路受早期环境事件的影响。当激活 CRF系统和伴随的内分泌、行为和自主神经系统 压力时期的反应显然是适应性的， 这些反应可能会导致严重的健康问题， 风险首先，在CRF激活过度或不必要的情况下， 延长。其次，在CRF激活响应于 无害的刺激事实上，CRF电路的失调将是 预计会对生物体产生广泛的影响。 有趣的是，CRF的中枢给药与垂体-肾上腺皮质激素相关。 肾上腺肥大，过度兴奋，焦虑，失眠，厌食， 动物的繁殖失败;所有症状都是 情感障碍我们预测，暴露于某些形式的早期 新生儿期的经验永久性地改变了CRF的神经 网络导致成年人对压力源的敏感性改变。因此在 在某些情况下（如剥夺母亲权利、身体虐待），这种影响 导致CRF系统内的过度活动， 对压力的敏感性在其他情况下，某些早期生活事件 (e.g.新生儿处理）似乎导致更有效的中枢神经系统调节 在适当条件下， 防止在以后的生活中发生病理学。

Conditions such as economic hardship and drug abuse often adversely affect child rearing patterns resulting severely compromised growth and development of the young. The results of epidemiological studies reveal that about one-half of abused children show neurological impairments. Furthermore, these rearing conditions serve as a major risk factor for subsequent patho- and psychphysiologies. Currently, little is known about the neurobiological consequences of altered child rearing patterns and of variations in early experience in general. The studies described in this application are designed to examine the effects of various forms of early experience on the development of neural systems that subserve an animal's response to stress in later life. We feel that this is an important endpoint, since the ability to successfully adapt to stressful stimuli is central to the health of the organism; perhaps increasing so for modern, industrialized societies. We will focus our studies on central corticotropin releasing factor (CRF) systems, as numerous studies implicate these circuits as important mediators of coordinated endocrine, autonomic nervous system and behavioral responses to stressors. The CRF- dense parvicellular paraventricular nucleus of the hypothalamus, which is the origin of the CRF terminal field in the neurohemal zone of the median eminence and the source of some efferents to autonomic centers in the brainstem, is ideally situated to coordinate the diverse adjustments necessary for surviving acute or chronic stressors. Recent evidence from our laboratories suggests that development of at least some central CRF circuits is regulated by early environmental events. While activation of CRF systems and the accompanying endocrine, behavioral, and autonomic responses during times of stress are clearly adaptive, there are conditions in which these same responses might provide a serious health risk. First, in instances where CRF activation is excessive or needlessly prolonged. Second, in instances where CRF activation occurs in response to innocuous stimuli. Indeed, dysregulation of the CRF circuitry would be expected to have wide-ranging consequences for the organism. Interestingly, central administration of CRF is associated with pituitary- adrenal hypertrophy, hyperarousal, anxiety, sleeplessness, anorexia, and reproductive failure in animals; all symptoms which are characteristic of affective disorders. We predict that exposure to certain forms of early experience during the neonatal period permanently alters the CRF neural network resulting in altered sensitivity to stressors as adults. Thus, in certain cases (e.g. maternal deprivation, physical abuse), this effect results in excessive activity within CRF systems and heightened sensitivity to stressors. In other instances, certain early life events (e.g. neonatal handling) appear to result in more efficient CNS regulation of CRF systems and, under appropriate conditions might prove to be protective against the occurrence of pathology in later life.