Prefrontal-Amygdala Interactions in Fear Extinction

恐惧消退中前额叶-杏仁核的相互作用

• 批准号: 7842175
• 负责人: Demetrio Sierra
• 金额: $ 3.84万
• 依托单位: UNIVERSITY OF PUERTO RICO MED SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7842175
• 关键词: Affect; Amygdaloid structure; Anesthesia procedures; Animal Model; Anxiety; Anxiety Disorders; Aversive Stimulus; Behavior; Behavioral; Biological Markers; Brain; Characteristics; Data; Development; Emotional; Emotions; Extinction (Psychology); Failure; Freezing; Fright; Human; Lead; Learning; Lesion; Measures; Medial; Memory; Muscimol; Neurons; Pharmaceutical Preparations; Phase; Physiological; Post-Traumatic Stress Disorders; Prefrontal Cortex; Procedures; Process; Psyche structure; Regulation; Research; Retrieval; Rodent; Role; Safety; Stimulus; Structure; Techniques; Testing; Time; Training; base; conditioned fear; learning extinction; neuromechanism; novel; physical conditioning; public health relevance; relating to nervous system; response

DESCRIPTION (provided by applicant): When emotions such as fear and anxiety are unregulated, several behaviors develop that are detrimental to mental and physical health. Such debilitating features are characteristic of anxiety disorders like post-traumatic stress disorder (PTSD). Biological markers of emotional regulation can be understood in an animal model involving Pavlovian fear conditioning and extinction. Fear extinction occurs when a tone that had been presented with an aversive stimulus is repeatedly presented in the absence of the stimulus. In humans, failure to extinguish fear responses is thought to contribute to PTSD and other anxiety disorders. Extinction, as a learning process, requires three phases: acquisition, consolidation, and retrieval. Recent evidence from rodent studies implicates the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) in extinction. It is unclear, however, when and how these structures interact during extinction. In Aim 1, we will determine in which phases of extinction training mPFC and BLA is necessary. This will be achieved by: 1) reversible inactivation of mPFC during different phases of extinction training; 2) reversible inactivation of BLA during different phases of extinction training. Once the critical phase of BLA-mPFC interaction is determined, Aim 2 will assess the contribution of BLA to tone-evoked and spontaneous neuronal activity in IL during extinction. This will be achieved by reversible inactivation of BLA while simultaneously recording neuronal activity in mPFC during extinction. Understanding the interaction of structures necessary for fear extinction could elucidate the mechanisms of emotional regulation. Deficiencies in these mechanisms may be the underlying factors in PTSD and other anxiety disorders. PUBLIC HEALTH RELEVANCE: In humans, the inability to extinguish fear responses is believed to be an underlying factor of anxiety disorders and post-traumatic stress disorder (PTSD). This research aims to understand how and when neural structures necessary for extinction interact. Deficiencies in the physiological mechanisms between the amygdala and prefrontal cortex could be rescued, thus reducing extinction failure. This could lead to novel treatments for extinction-based therapies for PTSD.

描述（由申请人提供）：当恐惧和焦虑等情绪得不到控制时，会产生一些对身心健康有害的行为。这种使人衰弱的特征是创伤后应激障碍（PTSD）等焦虑症的特征。情绪调节的生物标记可以在涉及巴甫洛夫恐惧条件反射和灭绝的动物模型中得到理解。恐惧消退发生时，一个音调已经出现了厌恶的刺激，在没有刺激的情况下反复出现。在人类中，无法消除恐惧反应被认为是导致创伤后应激障碍和其他焦虑症的原因。消隐作为一个学习过程，需要三个阶段：习得、巩固和检索。最近来自啮齿动物研究的证据暗示内侧前额叶皮层（mPFC）和基底外侧杏仁核（BLA）在灭绝中。然而，在灭绝期间，这些结构何时以及如何相互作用尚不清楚。在目标1中，我们将确定在哪个阶段的灭绝训练mPFC和BLA是必要的。这将通过：1)在消光训练的不同阶段对mPFC进行可逆失活；2)消光训练不同阶段BLA的可逆性失活。一旦确定了BLA- mpfc相互作用的关键阶段，Aim 2将评估BLA在IL消失期间对音调诱发和自发神经元活动的贡献。这将通过可逆的BLA失活来实现，同时在消失期间记录mPFC中的神经元活动。了解恐惧消退所必需的结构的相互作用可以阐明情绪调节的机制。这些机制的缺陷可能是创伤后应激障碍和其他焦虑症的潜在因素。