Extinction of Conditioned Behavior:A Deoxyglucose Study

描述（由申请人提供）：学习和记忆生理学的一个基本问题是了解灭绝和其他形式的行为抑制的神经机制。此外，由于巴甫洛夫条件反射会随着衰老和阿尔茨海默病而受损，因此对巴甫洛夫范式中消退效应的神经影像学研究也很有意义。巴甫洛夫条件反射后的消退过程是条件刺激（CS）在没有条件刺激（US）的情况下反复呈现的行为过程。这种消失过程导致条件行为的减少，即所谓的消失效应。在条件情绪反应（CER）范式中，对消退机制的更好理解也可能对在治疗情境中使用消退具有重要的临床意义，例如减少不必要的条件性恐惧。消除恐惧是公共卫生的一个主要问题。尽管许多关于消退的神经学研究暗示消退是习得的逆转，但自发恢复和解除抑制的行为现象表明情况并非如此，消退并不会导致大脑中CS-US关联的丧失或遗忘。具体目的是验证三个假设：1)灭绝与习得相反的假设，该假设预测灭绝涉及大脑中CS-US联想效应的丧失或遗忘；2)消退是一种情境学习的假设，即消退取决于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）的摄取来评估灭绝的脑代谢影响。实验大鼠的代谢数据将与暴露于相同音调的对照大鼠的代谢数据进行比较，以绘制在CER消失后对音调CS的反应中发生的区域脑活动变化。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）相关联。推测CER消退效应主要是由于CS-CER关联在前额叶皮层的神经表征受到抑制所致。相比之下，由于与CER抑制无关的CS-US联想效应的节省，在灭绝期间，其他神经回路的学习效应的逆转预计会很小。

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.