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 了解物种灭绝的神经机制。习得的行为 作为巴甫洛夫条件反射的结果可以通过 重复呈现条件刺激(CS)而不是 无条件刺激(美国)；这就是所谓的消退效应。 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，也就是 自发恢复和解除抑制表明情况并非如此。 而灭绝并不会导致CS的丧失或遗忘- 美国人在大脑中的联想。的行为训练范式 巴甫洛夫条件性抑制(条件性情绪反应，或 (CER程序)将在所有拟议研究中使用。大脑 生物灭绝对代谢的影响将通过摄取 氟脱氧葡萄糖(FDG)。实验大鼠的代谢反应 将与暴露在相同音调下的对照组大鼠进行比较 确定哪些区域活动变化是对音调的响应 CER消退后的条件刺激(CS)。此外，我们 将研究这些大脑代谢活动变化中的哪些是 与每个人的行为表现的变化相关 主题。具体目标是使用FDG脑图技术 为了检验三个假说：1)灭绝是 与习得相反，后者预测灭绝涉及 CS-US对大脑的联想效应的遗忘丧失；2) 灭绝类似于长期习惯化的假说，即 提示声调的CS突显将在听觉和听觉中受到调节。 觉醒系统；3)巴甫洛夫S关于灭绝是一种形式的假说 条件性反应的抑制。具体地说，它是 预测CER的消光效应是由于抑制了 前额叶皮质内CS-CER联系的神经表现 和中央杏仁核。相比之下，学习效果的逆转对 其他神经回路预计在灭绝期间是次要的，因为 CS-US联合效应的节省与CER抑制无关。 在CER范式中，对灭绝机制的更好理解可能 也具有重要的临床意义，如治疗用途 以减少不受欢迎的条件性恐惧。

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.