Anterograde Amnesia for Contextual Fear

描述(由申请人提供)：虽然海马区的必要性 某些类型的学习和记忆的形成在很大程度上是一致的， 海马体在情景恐惧条件反射中扮演的确切角色是 未知。拟议的项目基于一个理论模型，该模型是如何 在恐惧条件反射中，海马体与杏仁核相互作用。使用了该模型 以生成一组关于以下情况的预测 海马体开始参与上下文条件反射。此外，预测 是关于海马区手法的影响(解剖和 药理学)关于条件性恐惧的建立和表现。使用 一套连贯的操作和训练参数，拟议的研究 将评估该模型对恐惧条件反射现象的适用性。 首先，这些实验将建立海马区的时间分布。 参与其中。训练前和训练后的化学药品和 海马体的解剖完整性将揭示出 海马体是学习所必需的。其次，直接比较 电解性和兴奋性损伤将有助于深入了解两者之间的关系 在环境探索和语境处理之间。第三， 实验将检验海马区操作对脑电的影响 即刻电击不足，一种背景恐惧中与探索相关的损害 条件反射。最后，海马区的胆碱能神经支配 被操纵以确定其在逆行性和顺行性遗忘症中的作用 由海马区损伤产生。在实验的每个阶段，具体的 预测是基于对海马体完整性和 海马体-杏仁核相互作用中断。希望此外， 为调查获得性恐惧提供关键信息， 实验将为那些遭受疾病折磨的人提供洞察 海马区受损。

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.