Anterograde Amnesia for Contextual Fear

对情境恐惧的顺行性遗忘

• 批准号: 6796154
• 负责人: Michael S Fanselow
• 金额: $ 22.88万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-16 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6796154
• 关键词: amygdala; behavioral /social science research tag; conditioning; dissociative hysteria; experimental brain lesion; fear; hippocampus; laboratory rat; learning; learning disorders; mathematical model; memory disorders; model design /development; neural information processing; neuroanatomy; neurochemistry; neuronal transport; neurophysiology; performance

DESCRIPTION (provided by applicant): While the necessity of the hippocampal formation for some types of learning and memory largely is agreed upon, the exact role that the hippocampus plays in contextual fear conditioning is unknown. The proposed project is based on a theoretical model of how the hippocampus interacts with the amygdala in fear conditioning. The model is used to generate a set of predictions about the circumstances under which the hippocampus becomes involved in context conditioning. Furthermore, predictions are made regarding the effects of hippocampal manipulations (anatomical and pharmacological) on the establishment and performance of conditioned fear. With a cohesive set of manipulations and training parameters, the proposed studies will evaluate the model's applicability to fear conditioning phenomena. Firstly, the experiments will establish a temporal profile of hippocampal involvement. Pre- and post-training manipulations of the chemical and anatomical integrity of the hippocampus will reveal the points at which the hippocampus is necessary for learning. Secondly, a direct comparison of electrolytic and excitotoxic lesions will lend insight into the relationship between environmental explorations and context processing. Thirdly, the experiments will examine the effects of hippocampal manipulations on the immediate shock deficit, an exploration-related impairment in context fear conditioning. Finally, the cholinergic innervation of the hippocampus will be manipulated to determine its role in retrograde and anterograde amnesia produced by hippocampal lesions. At each stage in the experimentation, specific predictions are made based upon manipulations of hippocampal integrity and the disruption of hippocampus-amygdala interactions. It is hoped that, in addition to providing crucial information for the investigation of learned fear, the experiments will provide insight into the condition of those suffering from hippocampal damage.

描述（由申请人提供）：虽然海马的必要性 形成的某些类型的学习和记忆在很大程度上是一致的， 海马体在情境恐惧条件反射中的确切作用是 未知拟议的项目是基于一个理论模型， 海马体与杏仁核在恐惧条件反射中相互作用。利用该模型 来生成一组关于在何种情况下 海马体参与了情境调节。此外，预测 是关于海马操纵的影响（解剖和 药理学）对条件性恐惧的建立和表现的影响。与 一组连贯的操作和训练参数，建议的研究 将评估模型的适用性恐惧条件反射现象。 首先，实验将建立海马的时间轮廓， 参与。培训前和培训后的化学品操作， 海马体的解剖完整性将揭示 海马体是学习所必需的。第二，直接比较 电解质和兴奋性毒性损伤将有助于了解 环境探索和背景处理之间的联系三是 实验将检查海马操纵对大脑皮层的影响。 即时休克缺陷，一种与情境恐惧相关的探索性损伤 条件反射最后，海马体的胆碱能神经支配将被切断。 以确定其在逆行性和顺行性遗忘中的作用 由海马损伤引起的在实验的每一个阶段， 预测是基于对海马完整性和海马神经元的操纵来进行的。 破坏大脑皮层-杏仁核的相互作用。此外，希望 为了为调查习得性恐惧提供关键信息， 实验将提供深入了解那些患有 海马损伤