In search of a behaviorally plausible hippocampal model: Hippocampal subregional functions for encoding and retrieval of spatial memory

The hippocampus has been recognized as a central neural substrate for the acquisition and utilization of spatial memory. The current dissertation provides behavioral evidence for the differential involvement of different anatomical components (e.g., subregions) of the hippocampus in spatial learning and memory. The main problem addressed in the dissertation is how mnemonic information is encoded and retrieved via different subregions (i.e., CA3, CA1, and dentate gyrus-DG) of the hippocampus.; In Chapters 1–3, the hippocampal subregional mechanisms for spatial working memory were examined. The aim of Chapter 1 was to address the contribution of synaptic plasticity to the encoding vs. retrieval of spatial memory by reversibly inactivating N-methyl-D-aspartate receptors in different subregions with a spatial working memory paradigm. The aim of Chapter 2 was to confirm the results of the pharmacological manipulations of Chapter 1 by examining the effects of lesions of the subregions in the same behavioral task as well as to test some unanswered questions from Chapter 1. Finally, the aim of Chapter 3 was to study the interaction between the prefrontal cortex and the hippocampus in the same task to explain remaining questions from Chapters 1–2. In Chapter 4, the same issue was examined in a different behavioral paradigm (i.e., contextual fear-conditioning) with subregional lesions. Chapter 5 focused on specific mechanisms of encoding vs. retrieval within a particular hippocampal subregion (i.e., CA3) that have been suggested to play a vital role by computational models.; The major findings are that the CA3 subregion is the key to encoding of discrete mnemonic items and maintenance for short-term retrieval, whereas DG and CA1 subregions are more involved in retrieving the items after a long-term period. However, when a spatial environment entails an ill-defined spatial context rather than providing discrete cues and a task demands rapid acquisition of the spatial context, all the subregions seemed to be necessary for the initial acquisition of the contextual fear conditioning. These results were compared with traditional computational models for the hippocampal subregions and a behaviorally driven model was proposed for functional significance of hippocampal subcomponents based on these experimental data.