Stress, Prefrontal Cortex, and Decision Making (#4 of 14)

压力可以被定义为对一个人的心理和身体完整性的任何真实或感知的威胁 个体，尽管其短期适应价值，可导致行为，情感，认知，和 受影响个体中可能有害的免疫变化。此外，压力可以间接地导致 通过改变个体的行为策略来应对其他负面的健康后果。例如, 已有研究表明，压力会导致不良饮食、肥胖和药物滥用。一直以来 假设这种不适应行为可能是由于应激诱导的 前额叶皮质功能。先前关于压力引起的前额叶功能变化的研究表明， 前额叶皮质多巴胺和去甲肾上腺素的过量释放与工作记忆有关 减损。然而，压力对前额叶皮质决策功能的影响并没有 已经研究过了。特别是，冲动的选择是许多上瘾行为的强烈预测因素，例如 吸烟和药物滥用，这些都会因压力而加剧。因此，压力对冲动的影响 前额叶功能将是本项目的重点。在这项拟议的研究中，冲动将被量化 由于这种动物倾向于选择一个小的但立即的奖励，而不是一个大的但延迟的奖励. 一项跨期的选择任务。首先，将测试一种药物是否会增加冲动。 应激源，FG7142。第二，多巴胺能和/或去甲肾上腺素能通路在调节 冲动选择行为将使用受体特异性激动剂和拮抗剂进行测试。第三，我们将 检查这些药物操作如何影响神经过程中的价值折现 延迟性奖赏通过记录前额叶皮质神经元团的单个神经元活动 而且没有同样的药理操作。第四，使用离子导入和治疗相结合的方法 单神经元记录，将测试前额叶功能是否与冲动选择行为有关 被多巴胺和去甲肾上腺素通过直接作用于前额叶微电路而改变。 总体而言，这些实验的结果将提供关于细胞的关键信息 适应行为策略和正常前额叶功能中压力介导的损害的基础，以及 从而有助于开发针对应激中介的新的预防和治疗措施 疾病过程。

Stress can be defined as any real or perceived threat to the psychological and physical integrity of an individual, and despite its short-term adaptive value, can cause behavioral, emotional, cognitive, and immune changes in affected individuals that are potentially harmful. Furthermore, stress can indirectly lead to other negative health consequences by altering the behavioral strategies of the individuals. For example, it has been demonstrated that stress can lead to poor diet, obesity, and substance abuse. It has been hypothesized that such maladaptive behaviors might arise as a result of stress-induced weakening of the prefrontal cortical functions. Previous studies of stress-induced changes in prefrontal functions showed that excessive dopamine and norepinephrine release in prefrontal cortex contributed to working memory impairment. However, the effects of stress on the decision-making functions of the prefrontal cortex have not been studied. In particular, impulsive choice is a strong predictor for many addictive behaviors, such as smoking and substance abuse, that are exacerbated by stress. Therefore, the effect of stress on impulsivity and prefrontal functions will be the focus of this project. In the proposed study, impulsivity will be quantified by the animal's tendency to choose a small but immediate reward rather than a large but delayed reward in an inter-temporal choice task. First, it will be tested whether impulsivity is increased by a pharmacological stressor, FG7142. Second, the role of dopaminergic and/or noradrenergic pathways in the regulation of impulsive choice behavior will be tested using receptor specific agonists and antagonists. Third, we will examine how these pharmacological manipulations affect the neural process of discounting the value of delayed reward by recording the single-neuron activity of neuronal ensembles in the prefrontal cortex with and without the same pharmacological manipulations. Fourth, using the combination of iontophoresis and single-neuron recording, it will be tested whether prefrontal functions related to impulsive choice behaviors are altered by dopamine and norepinephrine through their direct actions on the prefrontal micro-circuitry. Overall, the results from these experiments will provide a critical piece of information regarding the cellular basis of stress-mediated impairments in adaptive behavioral strategies and normal prefrontal functions, and thereby contribute to the development of new preventive and therapeutic measures against stress-mediated disease processes.