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

压力可以被定义为任何真实的或感知到的对一个人的心理和身体完整性的威胁。 个体，尽管它的短期适应价值，可以导致行为，情感，认知， 受影响个体的免疫变化可能有害。此外，压力可能会间接导致 通过改变个体的行为策略来减少其他负面的健康后果。比如说， 已经证明，压力会导致不良饮食、肥胖和药物滥用。已经 假设这种适应不良的行为可能是由于压力引起的大脑功能的减弱而引起的。 前额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度释放有助于工作记忆 损伤然而，压力对前额叶皮层决策功能的影响还没有得到证实。 本文研究了特别是，冲动的选择是许多成瘾行为的一个强有力的预测因素，如 吸烟和药物滥用，这些都是由压力加剧。因此，压力对冲动的影响 和前额叶功能将是这个项目的重点。在拟议的研究中，冲动将被量化 动物倾向于选择一个小的，但立即奖励，而不是一个大的，但延迟奖励， 跨时选择任务首先，它将被测试是否冲动增加了药理学 应激源，FG 7142。第二，多巴胺能和/或去甲肾上腺素能通路在调节神经元凋亡中的作用。 将使用受体特异性激动剂和拮抗剂测试冲动选择行为。三是 研究这些药理学操作如何影响神经过程的价值折扣 通过记录前额叶皮层神经元集合的单神经元活动， 而且没有相同的药理学操作。第四，使用离子导入和 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 多巴胺和去甲肾上腺素通过它们对前额微回路的直接作用而改变。 总的来说，这些实验的结果将提供关于细胞的关键信息。 压力介导的适应性行为策略和正常前额叶功能障碍的基础，以及 从而有助于开发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.