AMYGDALA NEURONS AND FEAR CONDITIONING

杏仁核神经元和恐惧条件反射

• 批准号: 2599115
• 负责人: PATRICIA SHINNICK-GALLAGHER
• 金额: $ 18.25万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2599115
• 关键词: NMDA receptors; action potentials; amygdala; behavioral /social science research tag; biocytin; brain electrical activity; cell type; conditioning; electrostimulus; fear; glutamate receptor; laboratory rat; membrane potentials; neural transmission; synapses; voltage /patch clamp

DESCRIPTION (adapted from applicant's abstract): The amygdala is known to play a critical role in emotional responses particularly fear, in both humans and animals. The amygdala and its afferent and efferent connections comprise a major component of the auditory fear conditioning circuitry. The long-term objective of this research is to characterize pre- and postsynaptic modifications in amygdala glutamatergic neurotransmission underlying the expression of learned fear. Preliminary data show significant alterations in synaptic transmission in the internal capsule (IC) fiber pathway from the medial geniculate to the dorsal lateral amygdala recorded in vitro in amygdala slices from paired fear conditioned but not unpaired control animals. The proposed experiments using the fear-potentiated startle paradigm will test the hypothesis that lasting potentiation of synaptic transmission occurs at particular synapses within the fear conditioning intraamygdala circuitry. The following specific aims will be addressed using whole cell patch recording in amygdala slice preparations from three populations of animals. naive control, unpaired control and paired fear conditioned animals: 1) Characterize the modifications in synaptic transmission and membrane conductance underlying fear conditioning and determine the pre- and post-synaptic changes in N-methyl-D-aspartate (NMDA)- and non-NMDA-mediated synaptic transmission in animals exposed to a paired conditioned stimulus (CS) and aversive stimulus (UCS) with those exposed to the same information but in an unpaired paradigm and 2) trace the information flow through the amygdala by comparing in the three populations of animals the synaptic modifications occurring in glutamatergic transmission at different synapses in the amygdala fear conditioning circuitry. The results of the proposed experiments will enhance our understanding of the membrane mechanisms underlying emotional learning at the membrane and whole cell level and provide important information about changes in the essential elements of interneuronal communication within a key structure involved in emotion, the amygdala. Ultimately the proposed studies may provide insight into potential therapeutic strategies in the treatment of neuropsychiatric disorders such as anxiety, phobia, schizophrenia and in particular posttraumatic stress disorder.

描述（改编自申请人的摘要）：已知杏仁核 在情绪反应尤其是恐惧中发挥着关键作用 人类和动物。 杏仁核及其传入和传出连接 构成听觉恐惧调节电路的主要组成部分。 这 这项研究的长期目标是表征前和 杏仁核谷氨酸神经传递的突触后修饰 隐藏在习得性恐惧的表达之中。 初步数据显示 内囊突触传递的显着改变 (IC) 从内侧膝状体到背外侧杏仁核的纤维通路 体外记录在杏仁核切片中，来自成对的恐惧条件反射，但没有 未配对的对照动物。 建议的实验使用 恐惧增强的惊吓范式将检验持久的假设 突触传递的增强发生在特定的突触处 杏仁核内的恐惧调节回路。 具体目标如下 将使用杏仁核切片中的全细胞斑块记录来解决 来自三个动物种群的制剂。 幼稚控制，未配对 对照和配对恐惧条件动物：1）描述 突触传递和膜电导的改变 恐惧调节并确定突触前和突触后的变化 N-甲基-D-天冬氨酸 (NMDA) 和非 NMDA 介导的突触传递 暴露于配对条件刺激（CS）和厌恶刺激的动物 （UCS）与那些接触相同信息但处于不配对范式的人 2）通过比较来追踪通过杏仁核的信息流 三个动物群体中发生的突触修饰 杏仁核恐惧中不同突触的谷氨酸传递 调节电路。 拟议实验的结果将 增强我们对情绪背后的膜机制的理解 在膜和全细胞水平上学习并提供重要的 有关间神经元基本元素变化的信息 与情绪有关的关键结构——杏仁核内的交流。 最终，拟议的研究可能会深入了解潜在的 治疗神经精神疾病的治疗策略，例如 如焦虑症、恐惧症、精神分裂症，特别是创伤后应激障碍 紊乱。