Lateralization of Emotional Memory Circuits in Amygdala

杏仁核情绪记忆回路的偏侧化

• 批准号: 7094518
• 负责人: HUGH T BLAIR
• 金额: $ 18.26万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7094518
• 关键词: amygdala; behavioral /social science research tag; brain mapping; cerebral dominance; conditioning; discrimination learning; electrophysiology; electrostimulus; enzyme activity; eyelids; fear; immunocytochemistry; laboratory rat; leg; memory; mitogen activated protein kinase; neural information processing; neural plasticity; phosphorylation; psychopharmacology; sensorimotor system

DESCRIPTION (provided by applicant): "Fear" is an emotion that can be aroused by a predictive stimulus that warns of impending danger, such as the growl of a predator or the sight of an angry face. But most of the stimuli we encounter in our environment are non-threatening, so how do we discriminate stimuli that predict danger from those that do not? Learning to recognize danger depends upon the amygdala, a cluster of nuclei in the brain's temporal lobe. When the amygdala is damaged, people and animals are impaired at recognizing stimuli that predict danger. Conversely, overactivation of the amygdala can lead to excessive fear of non-threatening stimuli and may contribute to disorders such as phobias, chronic anxiety, depression, and post-traumatic stress. A better understanding of the amygdala's role in fear learning may thus provide the key to improving diagnosis and treatment for mental disorders characterized by symptoms of fear and anxiety. The experiments proposed here will pursue a novel approach to studying the amygdala's role in fear learning by using a new procedure that allows fear memories to be stored by one hemisphere of the amygdala and not the other. A recent study by the investigator has shown that when rats are trained to fear a noise by pairing it with electric shock delivered to one eyelid, learning to fear the noise depends upon the amygdala contralateral but not ipsilateral from the shocked eyelid. This discovery reveals that the amygdala's fear circuitry is functionally lateralized, so that fear memories about stimuli that predict threats to one side of the body can be represented mainly within the amygdala of the opposite brain hemisphere. An integrated program of behavioral, electrophysiological, and immunostaining experiments will exploit this lateralization to investigate the functional architecture of the amygdala's fear circuitry. First, anatomical pathways that convey information about aversive stimuli to the amygdala will be identified. Second, studies will test the hypothesis that fear memories are stored in the amygdala by synaptic changes triggered by convergence of sensory information about neutral and aversive stimuli. Third, studies will determine whether the left and right hemispheres of the amygdala exert opponent control over lateralized defensive behaviors. Findings from these experiments will help to resolve critical questions about the amygdala's role in learning, memory, and emotions, and thereby pave the way for improving future diagnosis and treatment of anxiety disorders.

描述（由申请人提供）：“恐惧”是一种可以由警告即将发生的危险的预测性刺激引起的情绪，例如捕食者的咆哮或看到愤怒的面孔。但我们在环境中遇到的大多数刺激都是非威胁性的，那么我们如何区分预测危险的刺激和不预测危险的刺激呢？学习识别危险取决于杏仁核，杏仁核是大脑颞叶中的一组核。当杏仁核受损时，人和动物识别预测危险的刺激的能力就会受到损害。相反，杏仁核过度激活会导致对非威胁性刺激的过度恐惧，并可能导致恐惧症、慢性焦虑、抑郁和创伤后应激障碍等疾病。因此，更好地了解杏仁核在恐惧学习中的作用可能为改善以恐惧和焦虑症状为特征的精神障碍的诊断和治疗提供关键。这里提出的实验将寻求一种新的方法来研究杏仁核在恐惧学习中的作用，通过使用一种新的程序，允许恐惧记忆由杏仁核的一个半球而不是另一个半球存储。研究人员最近的一项研究表明，当通过将噪音与对一侧眼睑的电击配对来训练老鼠害怕噪音时，学会害怕噪音取决于对侧杏仁核，而不是受电击眼睑的同侧杏仁核。这一发现揭示了杏仁核的恐惧回路在功能上是偏侧化的，因此关于预测身体一侧受到威胁的刺激的恐惧记忆可以主要在另一侧大脑半球的杏仁核中表现出来。行为、电生理学和免疫染色实验的综合程序将利用这种偏侧化来研究杏仁核恐惧回路的功能结构。首先，将确定向杏仁核传递有关厌恶刺激的信息的解剖路径。其次，研究将检验这样的假设：恐惧记忆是通过中性和厌恶刺激的感觉信息汇聚引发的突触变化而存储在杏仁核中的。第三，研究将确定杏仁核的左右半球是否对侧化防御行为施加对手控制。这些实验的结果将有助于解决有关杏仁核在学习、记忆和情感中的作用的关键问题，从而为改善未来焦虑症的诊断和治疗铺平道路。