Schema and memory consolidation

Abstract

The traditional view of systems memory consolidation is that it is a gradual process that takes place over days or weeks. Within this approach, the hippocampus (HPC) is thought to be involved in the rapid encoding of specific events, whilst neocortex is thought to be involved in slow learning. An idea posited recently is that systems consolidation can occur rapidly if an appropriate “schema” into which the new information can be incorporated has been previously created. Using a hippocampaldependent paradigm, rats were trained to learn a schema involving 6 flavour-place paired-associates (PAs). Once the schema was acquired, relevant new information then became assimilated into extra-hippocampal regions and rapidly became hippocampal-independent. Building upon this foundation and the PAs schema paradigm, this thesis has explored several aspects of the neurobiology of schemas in animals. The first part of the thesis examined the importance of a relevant schema in new information processing. Rats were trained in both a consistent and inconsistent schema. In the consistent schema, rats could learn new PAs in a single trial; however, in the inconsistent schema, rats failed to learn the new PAs as they had not established an appropriate schema that could facilitate rapid learning. The second part of the thesis investigated the role of hippocampal NMDA receptors and dopamine receptors during encoding of new PAs. Bilateral hippocampal infusion of either the NMDA receptor antagonist D-AP5 or the D1/D5 dopamine receptor antagonist SCH23390 before encoding of new PAs resulted in impaired memory tested at 24 hr. This result suggests that the encoding of new PAs is dependent upon NMDA receptors in the HPC and also that dopamine is involved in the modulation of encoding new PAs. The final chapters of the thesis attempted to identify the extrahippocampal regions in which these new PAs are integrated with the schema during encoding. To identify the regions that may be involved, immediate early genes (Zif268 and Arc) were used. In a group of cortical structures, including the prelimbic cortex, there was significantly higher Zif268 and Arc expression when encoding 2 new PAs compared to the reactivation of previously learned (original) PAs or the encoding of 6 new PAs. These findings indicate that the prelimbic cortex may be critical for rapid assimilation of new information into a pre-existing schema. Finally, the last experiment in the thesis investigated this finding using bilateral microinfusions of either the AMPA receptor antagonist CNQX or the NMDA receptor antagonist D-AP5 into the prelimbic cortex. Infusions of CNQX and D-AP5 resulted in poor learning of the new PAs in the schema task. This indicates that parallel encoding of new PAs occurred in the prelimbic cortex and the HPC. The experimental results presented in this thesis suggest that the prelimbic cortex, in particular, plays a crucial role along with the HPC during encoding of new information in rapid memory formation.