Extinction of Conditioned Behavior:A Deoxyglucose Study

描述(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亡和其他形式的行为抑制的神经机制。此外，巴甫洛夫范式中消退效应的神经成像研究很有意义，因为巴甫洛夫条件反射随着年龄的增长和阿尔茨海默病的出现而受损。巴甫洛夫条件反射后的消退过程是一种重复呈现条件刺激(CS)而不呈现无条件刺激(US)的行为过程。这种灭绝过程导致条件性行为的减少，这就是所谓的灭绝效应。在条件化情绪反应(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，例如减少不受欢迎的条件性恐惧。解除恐惧是公共卫生中的一个主要问题。虽然许多关于灭绝的神经研究表明，灭绝是习得的逆转，但自发恢复和去抑制的行为现象表明情况并非如此，灭绝不会导致大脑中CS-US联系的丧失或遗忘。具体目的是检验三个假说：1)消亡是习得的对立面，它预测消亡涉及CS-US对大脑的联想效应的丧失或遗忘；2)消亡是语境学习的一种形式，它表明消亡取决于来自CS和语境的神经输入；以及3)巴甫洛夫的假说，消亡是对条件性反应的一种抑制形式。将通过摄取氟脱氧葡萄糖(FDG)来评估消光对脑代谢的影响。实验大鼠的代谢数据将与暴露在相同音调下的对照组大鼠进行比较，以绘制出在CER消失后响应音调CS的局部脑活动变化。大脑代谢：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。推测CER的消退作用主要是由于抑制了前额叶皮质CS-CER联系的神经表征。相反，由于与CER抑制无关的CS-US联合效应的保存，在灭绝期间，其他神经回路上学习效应的逆转预计是很小的。

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.