Fear and Natural Risky Decisions in Rats

老鼠的恐惧和自然的危险决定

• 批准号: 9095450
• 负责人: Jeansok John Kim
• 金额: $ 36.32万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-15 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9095450
• 关键词: Address; Affective; Amygdaloid structure; Animal Behavior; Animal Experimentation; Animals; Anxiety Disorders; Area; Behavior; Brain; Cells; Clinical; Cognitive Therapy; Conflict (Psychology); Data; Decision Making; Disease; Disinhibition; Environment; Evaluation; Food; Freezing; Fright; Goals; Health; Hippocampus (Brain); Human; Knowledge; Learning; Lesion; Life; Maintenance; Medial; Mediating; Modeling; Movement; Neurons; Panic; Pattern; Pharmaceutical Preparations; Phobias; Play; Post-Traumatic Stress Disorders; Prefrontal Cortex; Preparation; Process; Psychopathology; Rattus; Research; Risk; Risk Assessment; Risk Behaviors; Robot; Robotics; Role; Safety; Scanning; Series; Shapes; Structure; System; Testing; Time; base; conditioned fear; fear memory; generalized anxiety; innovation; insight; motivated behavior; neural circuit; neuromechanism; novel; pre-clinical; programs; regional difference; relating to nervous system; research study; response; screening

DESCRIPTION (provided by applicant): While fear plays a fundamental, protective role in our lives, irrational and uncontrollable fear responses are common features of various anxiety disorders that are detrimental to one's quality of daily life. Most contemporary views on fear ascribe preeminent importance to learning, and decades of animal research using the Pavlovian fear conditioning paradigm have made tremendous progress in identifying the neural circuits and mechanisms responsible for the acquisition, maintenance and expression of conditioned fear memories, with a general focus on the amygdala. In contrast to learned fear, innate fear and its effects on risky decisions have largely been overlooked in preclinical and clinical fear research despite its evolutionarily-conserved role in survival. We have recently found that the amygdala regulates both innate fear responses and risky behavior in rats foraging in a seminaturalistic environment with a 'predator-like' robot that is programmed to surge toward the animal as it seeks food. By applying naturalistic 'prey-predator' interactions, the long-term goal of this research is to construct a general experimental and theoretical basis for understanding the functions of fear in ecologically-relevant situations that closely reflect the environments in which fear responses and risky decisions naturally occur. We will incorporate this in a systems-level fear model that can fill the gaps in knowledge, predict new results, and provide insights into the basic approach-avoid conflicts that are thought to underlie human psychopathologies. There are three specific aims of the project: (1) a BEHAVIORAL ANALYSIS will investigate the basic rules of the rat's natural foraging decision in highly quantifiable 'approach food-avoid predator' situations; (2) a SYSTEMS-LEVEL ANALYSIS will reveal the specific roles that the amygdala, medial prefrontal cortex, and hippocampus play in mediating innate fear and risky foraging behavior; and (3) a NEURAL RECORDING ANALYSIS will relate specific components of the animal's behavior to a neural representation of dynamic, affective evaluation in real time. Information generated from this project would be of significance (1) from a basic scientific perspective, providing a more complete picture of fearful behavior in an ecologically-realistic environment; and (2) from an applied perspective, providing insights into developing (and screening the safety of) drug and cognitive- behavioral therapies for generalized anxiety, panic, phobia and posttraumatic stress disorders.

描述（由申请人提供）：虽然恐惧在我们的生活中起着基本的保护作用，但不合理和无法控制的恐惧反应是各种焦虑症的常见特征，这些特征不利于人们的日常生活质量。大多数当代关于恐惧的观点对学习归功于学习的重要性，并且使用Pavlovian恐惧调节范式进行了数十年的动物研究，在确定造成有条件的恐惧记忆的神经回路和机制方面取得了巨大进步，并以对杏仁核的一般关注。与学习的恐惧相反，临床前和临床恐惧研究中的天生恐惧及其对风险决定的影响在很大程度上被忽略了，尽管它在生存中得到了进化的作用。最近，我们发现，杏仁核调节了在享受的恐惧反应和危险行为中，在半自然主义环境中觅食的大鼠具有“捕食者样”机器人的觅食，该机器人被编程为在寻求食物时向动物涌动。通过运用自然主义的“猎物”互动，这项研究的长期目标是建立一个一般的实验和理论基础，以理解与生态相关的情况下恐惧的功能，这些情况紧密反映了恐惧反应和自然发生的恐惧反应和风险决定的环境。我们将将其纳入系统级的恐惧模型中，该模型可以填补知识的空白，预测新的结果，并提供有关人类精神病理学基础的基本避免方法冲突的见解。 该项目有三个具体的目的：（1）行为分析将调查大鼠在高度量化的“进食食物避免食物捕食者”情况下的自然觅食决策的基本规则； （2）系统级分析将揭示杏仁核，内侧前额叶皮层和海马在介导先天性的恐惧和风险觅食行为中发挥的特定作用； （3）神经记录分析将将动物行为的特定组成部分与实时动态，情感评估的神经表示。 从基本的科学角度来看，从该项目产生的信息将具有重要意义（1），从而为在生态现实的环境中提供了更完整的恐惧行为； （2）从应用的角度来看，提供了开发（并筛选）药物和认知行为疗法的洞察力，以实现普遍的焦虑，恐慌，恐惧症和创伤后应激障碍。