Fear and Natural Risky Decisions in Rats

老鼠的恐惧和自然的危险决定

基本信息

批准号：
10363693
负责人：
Jeansok John Kim
金额：
$ 38.6万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-15 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10363693
关键词：
Address Amygdaloid structure Animals Area Behavior Behavioral Behavioral Mechanisms Behavioral Paradigm Biological Biological Models Body Regions Brain Cell Nucleus Clinical Complement Complex Dangerousness Decision Making Dorsal Elements Environment Evolution Exhibits Food Freezing Fright Genetic Goals Grant Health Care Costs Helping Behavior Hippocampus (Brain)Human Knowledge Lead Lesion Life Location Maintenance Maps Medial Mediating Midbrain structure Modeling Motion Nature Neurobiology Neurons Nociception Organism Pain Panic Pathway interactions Pharmacology Phobias Play Population Post-Traumatic Stress Disorders Predatory Behavior Prefrontal Cortex Process Psychopathology Rattus Research Risk Risk Assessment Robot Rodent Role Safety Sampling Shapes Signal Pathway Signal Transduction Stimulus Structure System Techniques Testing Time Translating United States Update Work base conditioned fear driving force effective therapy expectation experience experimental study fear memory generalized anxiety innovation insight midbrain central gray substance neuromechanism novel optogenetics programs response virtual

项目摘要

PROJECT SUMMARY Basic fear research largely employs the Pavlovian fear conditioning paradigm in rodents. While this model systems approach simplifies behavioral and biological analyses of acquisition, maintenance and expression mechanisms of conditioned fear memories, fear conditioning studies cannot address the fact that animals and humans rely on a multitude of actions and decisions to survive the breadth of risky situations in the real world. Hence, there is a need to complement fear conditioning studies with ecologically-relevant fear research that can lead to novel translational insights. This renewal application will continue to employ and enhance our ‘approach food-avoid predator’ paradigm to investigate the naturalistic workings of the brain’s fear system. Specifically, in Aim 1, we will examine how rats adapt their fear responses, risk-assessment and foraging decisions to more realistic and diverse risky situations by simulating hidden versus visible threats and terrestrial versus aerial predators. We will also determine the functions of fear conditioning, which has never been analyzed in a naturalistic setting, under realistic prey-predator interaction scenarios. In Aim 2, we will utilize pharmacology, single unit recordings and optogenetics to further elaborate the neural mechanisms of fear in naturalistic risky conditions. Based on our earlier work, we hypothesize that the dorsal periaqueductal gray-amygdala pathway signals impending threats to elicit innate fear, that the reciprocal medial prefrontal cortex-amygdala circuits serve risk proximity assessment functions, and that the amygdala-hippocampal pathway provides the safety-danger boundary information for adaptive foraging decisions and strategies. This ethologically relevant project is significant (i) from a basic scientific perspective because it will advance a more naturalistic view of the fear system that will fill gaps in knowledge and predict new results, and (ii) from an applied perspective because it can lead to novel insights to develop more effective treatments for generalized anxiety, panic, phobia and posttraumatic stress disorders.

项目摘要基本的恐惧研究在很大程度上采用了啮齿动物中的帕夫洛维亚恐惧调节范式。而这个模型系统方法简化了采集，维护和表达的行为和生物学分析有条件的恐惧记忆机制，恐惧调节研究无法解决动物和人类依靠多种行动和决定来在现实世界中的风险状况范围内生存。因此，有必要通过与生态上的恐惧研究相辅相成可以导致新颖的翻译见解。此更新申请将继续雇用并增强我们的 “接近食物避免食物的捕食者”范式调查大脑恐惧系统的自然作品。具体而言，在AIM 1中，我们将研究老鼠如何适应其恐惧反应，风险评估和觅食通过模拟隐藏的威胁与可见威胁和陆地与空中捕食者。我们还将确定恐惧调节的功能，这从来没有在逼真的猎物互动场景下，我们已经在自然主义的环境中进行了分析。在AIM 2中，我们将使用药理学，单位记录和光遗传学进一步阐述在自然主义的危险条件下恐惧。基于我们较早的工作，我们假设背侧围位灰色 - 杏仁核路径的信号即将引起天生恐惧的威胁，互惠前额叶 Cortex-Amygdala电路具有风险接近评估功能，并且是杏仁核-Hippocampal 途径为自适应觅食决策和策略提供了安全破坏者边界信息。这从基本的科学角度来看，与伦理学相关的项目具有重要意义（i），因为它将进一步发展恐惧系统的自然主义观点将填补知识的空白并预测新结果，（ii）应用的观点是因为它可以导致新颖的见解，以开发更有效的疗法焦虑，恐慌，恐惧症和创伤后应激障碍。