EARLY EXPERIENCE ALTERS ADULT BEHAVIOR AND THE HPA AXIS

经济困难和滥用药物等条件往往会对 儿童养育模式导致严重损害生长和 青少年的发展。流行病学研究的结果显示 大约一半的受虐儿童表现出神经损伤。 此外，这些养育条件也是一个主要风险因素 随后的病态和心理生理学。目前，人们对此知之甚少。 改变孩子的养育方式和 一般情况下早期经验的变化。在这篇文章中描述的研究 应用程序旨在检查各种形式的早期 开发为动物神经系统服务的经验 在晚年生活中对压力的反应。我们觉得这是一个重要的 终点，因为成功适应应激刺激的能力是 对生物体的健康至关重要；也许对现代生物来说， 工业化社会。我们的研究将集中在中环 促肾上腺皮质激素释放因子(CRF)系统 将这些回路牵连为协调内分泌的重要媒介， 自主神经系统和对应激源的行为反应。CRF- 致密的下丘脑室旁核，这是 CRF终末野在正中神经血缘的起源 突起与某些自主中枢传出神经的来源 脑干，是协调各种调整的理想位置 在急性或慢性应激源中生存所必需的。最近的证据来自 我们的实验室表明，至少有一些中枢性慢性肾衰的发生 电路受早期环境事件的调节。在激活时 CRF系统及其伴随的内分泌、行为和自主神经 在压力时期的反应显然是自适应的，有 这些同样的反应可能会带来严重健康的情况 风险。首先，在CRF激活过多或不必要的情况下 延长了。第二，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的中枢给药与脑下垂体- 肾上腺肥大、高觉醒、焦虑、失眠、食欲不振和 动物的繁殖失败；所有的症状都是 情感障碍。我们预测，接触某些形式的早期 新生儿期的经历永久性地改变CRF神经 网络导致成年后对应激源的敏感度改变。因此，在 某些情况(例如，剥夺产妇、身体虐待)，这种影响 导致CRF系统内过度活动，并导致 对压力源的敏感性。在其他情况下，某些早期生活事件 (例如，新生儿处理)似乎导致更有效的中枢神经系统调节 在适当的条件下，可能被证明是 在以后的生活中防止病理的发生。

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.