Anterograde Amnesia for Contextual Fear

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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.