EXTINCTION OF CONDITIONED BEHAVIOR--A DEOXYGLUCOSE STUDY

学习和记忆的神经生物学中的一个基本问题是 了解灭绝的神经机制 后天行为 因为巴甫洛夫条件反射的结果， 重复呈现条件刺激（CS），而不 无条件刺激（US）;这被称为消光效应。 尽管许多关于灭绝的神经活动研究表明， 灭绝是获得的逆转， 自发恢复和去抑制表明情况并非如此 而这种灭绝并不会导致CS的丧失或遗忘， 美国在大脑中的联系。 行为训练范式 巴甫洛夫条件性抑制（条件性情绪反应，或 CER程序）将用于所有拟定研究。 大脑 将通过摄取以下物质来评估消退的代谢效应： 氟脱氧葡萄糖（FDG）。 实验大鼠的代谢反应 将与暴露于相同音调的对照大鼠进行比较， 识别响应于所述音调而发生哪些区域活动变化 条件刺激（CS）消失后的CER。 另外我们 将检查哪些大脑代谢活动变化 与每个人的行为表现的变化相关， 话题吧 具体目标是使用FDG脑标测技术 为了检验三个假设：1）灭绝是人类灭绝的假设。 与获得相反，它预测灭绝涉及 丧失对CS-US对大脑的联想效应的遗忘; 2） 假设灭绝类似于长期习惯化， 表明，CS的声调的显着性将调制在听觉和 唤醒系统; 3）巴甫洛夫的假设，即灭绝是一种形式 条件反射的抑制。 具体来说就是 预测CER消光效应是由于抑制了 前额叶皮层中CS-CER关联的神经表征 和中央杏仁核 相反，学习效果的逆转， 其他神经回路预计在灭绝期间是次要的， 与CER抑制无关的CS-US联合效应的节省。 在CER范例中，更好地理解灭绝机制可能 也有重要的临床意义，如治疗用途， 来减少不必要的条件性恐惧。

A fundamental problem in the neurobiology of learning and memory is understanding the neural mechanisms of extinction. Behavior acquired as the result of Pavlovian conditioning can be extinguished by presenting the conditioned stimulus (CS) repeatedly without the unconditioned stimulus (US); this is known as the extinction effect. Although many neural activity studies of extinction imply that extinction is the reversal of acquisition, the behavioral phenomena of spontaneous recovery and disinhibition suggest that this is not the case and that extinction does not result in the loss or unlearning of the CS- US association in the brain. The behavioral training paradigm of Pavlovian conditioned suppression (conditioned emotional response, or CER procedure) will be used in all the proposed studies. The brain metabolic effects of extinction will be assessed with uptake of fluorodeoxyglucose (FDG). Metabolic responses from experimental rats will be compared to those of control rats exposed to the same tone to identify which regional activity changes occur in response to the tone conditioned stimulus (CS) after extinction of the CER. In addition, we will examine which of these brain metabolic activity changes are correlated with variations in the behavioral performance of each subject. The specific aims are to use the FDG brain mapping technique to test three hypotheses: 1) The hypothesis that extinction is the opposite of acquisition, which predicts that extinction involves the loss of unlearning of the CS-US associative effects on the brain; 2) The hypothesis that extinction is similar to long-term habituation, which suggests that CS salience of the tone will be modulated in auditory and arousal systems; and 3) Pavlov s hypothesis that extinction is a form of inhibition of the conditioned response. Specifically, it is predicted that the CER extinction effect is due to the inhibition of the neural representation of the CS-CER association in the prefrontal cortex and central amygdala. In contrast, reversals of learning effects on other neural circuits are expected to be minor during extinction due to the savings of CS-US associative effects unrelated to CER inhibition. In the CER paradigm, a better understanding of extinction mechanisms may also have important clinical implications, such as the therapeutic use of extinction to reduce undesired conditioned fears.