Extinction of Conditioned Behavior:A Deoxyglucose Study

描述（由申请人提供）：学习和记忆生理学中的一个基本问题是理解消退和其他形式的行为抑制的神经机制。此外，巴甫洛夫范式中的消退效应的神经影像学研究是令人感兴趣的，因为巴甫洛夫条件反射随着年龄的增长和阿尔茨海默病而受损。巴甫洛夫条件反射后的消退过程是一种行为过程，其中条件刺激（CS）重复呈现而无非条件刺激（US）。这种灭绝过程导致条件行为的下降，称为灭绝效应。在条件性情绪反应（CER）范式中，更好地理解消退机制也可能对在治疗情况下使用消退具有重要的临床意义，例如减少不希望的条件性恐惧。消除恐惧是公共卫生的一个主要问题。虽然许多神经学的研究表明，灭绝是收购的逆转，自发恢复和去抑制的行为现象表明，这是不是这样，灭绝不会导致在大脑中的CS-US协会的损失或遗忘。具体的目的是检验三个假设：1）灭绝与习得相反的假设，该假设认为灭绝涉及大脑中CS-US联想效应的丧失或遗忘; 2）灭绝是一种情境学习的假设，该假设认为灭绝依赖于来自CS和情境的神经输入; 3）巴甫洛夫的假设，即消退是条件反应的一种抑制形式。将通过氟脱氧葡萄糖（FDG）的摄取来评价消退的脑代谢效应。将来自实验大鼠的代谢数据与暴露于相同音调的对照大鼠的代谢数据进行比较，以绘制CER消退后响应于音调CS而发生的局部脑活动变化。脑代谢：活动（FDG数据）也将与每个受试者在训练和测试期间的行为表现（行为数据）相关。据预测，CER消退效应主要是由于抑制的CS-CER协会在前额叶皮层的神经表征。相反，由于与CER抑制无关的CS-US关联效应的节省，预期在消退期间对其他神经回路的学习效应的逆转是轻微的。

DESCRIPTION (provided by applicant): A fundamental problem in the physiology of learning and memory is to understand the neural mechanisms of extinction and other forms of behavioral inhibition. In addition, neuroimaging investigations of extinction effects in Pavlovian paradigms are of interest because Pavlovian conditioning is impaired with aging and in Alzheimer's disease. An extinction procedure after Pavlovian conditioning is a behavioral procedure in which the conditioned stimulus (CS) is repeatedly presented without the unconditioned stimulus (US). This extinction procedure results in a decline in conditioned behavior that is known as an extinction effect. In the conditioned emotional response (CER) paradigm, a better understanding of extinction mechanisms may also have important clinical implications for using extinction in therapeutic situations, such as reduction of undesired conditioned fears. Relief from fear is a major concern in public health. Although many neural 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 specific aims are to test three hypotheses: 1) The hypothesis that extinction is the opposite of acquisition, which predicts that extinction involves the loss or unlearning of the CS-US associative effects on the brain; 2) The hypothesis that extinction is a form of contextual learning, which suggests that extinction depends on neural input from both the CS and the context; and 3) Pavlov's hypothesis that extinction is a form of inhibition of the conditioned response. The brain metabolic effects of extinction will be evaluated with uptake of fluorodeoxyglucose (FDG). Metabolic data from experimental rats will be compared to those of control rats exposed to the same tone to map regional brain activity changes occurring in response to the tone CS after extinction of the CER. Brain metabolic : activity (FDG data) will also be correlated with the behavioral performance of each subject during training and testing sessions (behavioral data). It is predicted that the CER extinction effect is mainly due to the inhibition of the neural representation of the CS-CER association in the prefrontal cortex. 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.