Neural basis of active avoidance behavior

主动回避行为的神经基础

基本信息

批准号：
8876788
负责人：
Manuel A Castro-Alamancos
金额：
$ 38.63万
依托单位：
DREXEL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-19 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8876788
关键词：
Address Air Amygdaloid structure Animals Anxiety Disorders Autonomic nervous system Aversive Stimulus Avoidance Learning Basal Ganglia Behavior Behavioral Cell Nucleus Cells Conditioned Reflex Conditioned Stimulus Corpus striatum structure Emotional Event Freezing Fright Goals Health Heart Rate Human Lateral Learning Lesion Mediating Mental disorders Midbrain structure Modality Modeling Outcome Output Pathological anxiety Pathway interactions Pedunculopontine Tegmental Nucleus Performance Phobias Post-Traumatic Stress Disorders Procedures Process Ramp Rattus Research Research Project Grants Role Sensory Signal Transduction Social Phobia Staging Stimulus Structure Substantia nigra structure Testing Thalamic structure Transportation Work avoidance behavior base behavioral response cholinergic clinically relevant conditioned fear conditioning coping laterodorsal tegmentum learned behavior midbrain central gray substance neural circuit rapid detection relating to nervous system response sensory stimulus social social anxiety social situation superior colliculus Corpora quadrigemina

项目摘要

DESCRIPTION (provided by applicant): Enormous progress has been made about the neural substrates of Pavlovian fear conditioning. In this paradigm, the association between an initially neutral sensory stimulus with an aversive event (footshock) leads to the transformation of the neutral stimulus into a conditioned stimulus (CS) that elicits fear responses in the form of immobility, potentiated startle, changes in heart rate, etc, which were not evoked by the neutral sensory stimulus. Ample evidence indicates that the CS must be transmitted through the modality-specific sensory thalamus to reach emotional processing centers in the amygdala, where the association with the aversive stimulus occurs and an output drives the conditioned responses. In contrast, little is known about the neural circuits involved in active avoidance behavior. In this paradigm, subjects learn to avoid an aversive event by producing an appropriate behavioral response (avoidance) during an interval signaled by the presentation of a CS. Understanding active avoidance behavior is important because it is present in most forms of pathological anxiety. Recently, using rats we found that lesions of the sensory thalamus that abolish Pavlovian fear conditioning to the modality-related CS do not abolish active avoidance to the same CS. In these animals, the superior colliculus processes the CS and mediates active avoidance. Our general hypothesis is that the superior colliculus serves as an early relay station for rapid detection of sensory signals that are behaviorally significant and require immediate action; an early sensorimotor hub well suited to mediate active avoidance. With this work as a backdrop, we have developed a hypothetical model of the neural circuits involved in the performance (expression) of active avoidance behavior. Here we propose to test two key aspects of this model. The first goal is to determine the output pathways that mediate active avoidance. The second goal is to determine the role of basal ganglia in gating active avoidance responses. We will employ a combination of behavioral, electrophysiological, pharmacological and histological procedures to reach these goals. The long term objective of this research project is to reveal the neural substrates of active avoidance behavior, which has direct relevance to many psychiatric disorders.

描述（由申请人提供）：关于巴甫洛夫恐惧条件反射的神经基础已经取得了巨大进展。在这个范式中，最初中性的感觉刺激与厌恶事件（足部电击）之间的关联导致中性刺激转变为条件刺激（CS），从而引发以不动、增强惊吓、心脏变化等形式的恐惧反应。率等，这些不是由中性感觉刺激引起的。充足的证据表明，CS 必须通过特定模态的感觉丘脑传输，到达杏仁核的情绪处理中心，在那里与厌恶刺激发生关联，并产生输出驱动条件反应。相比之下，人们对主动回避行为所涉及的神经回路知之甚少。在这种范式中，受试者在 CS 呈现信号的时间间隔内通过产生适当的行为反应（回避）来学习避免厌恶事件。了解主动回避行为很重要，因为它存在于大多数形式的病理性焦虑中。最近，我们在大鼠身上发现，感觉丘脑的损伤消除了对模态相关 CS 的巴甫洛夫恐惧条件反射，但并不能消除对相同 CS 的主动回避。在这些动物中，上丘处理 CS 并介导主动回避。我们的一般假设是，上丘充当早期中继站，用于快速检测具有行为意义并需要立即采取行动的感觉信号；非常适合调节主动回避的早期感觉运动中枢。以这项工作为背景，我们开发了一个涉及主动回避行为表现（表达）的神经回路的假设模型。在这里，我们建议测试该模型的两个关键方面。第一个目标是确定介导主动回避的输出途径。第二个目标是确定基底神经节在门控主动回避反应中的作用。我们将结合行为、电生理学、药理学和组织学程序来实现这些目标。该研究项目的长期目标是揭示主动回避行为的神经基础，该行为与许多精神疾病直接相关。