A Synaptic and Systems Level Investigation of Memory Processes Using a Novel Multiple Memory Behavioural Procedure

It is proposed that memories stabilize through synaptic and systems level consol- idation processes, forming long-lasting memory representations. Systems con- solidation models suggest that hippocampal contribution to memory storage dis- engages as time progresses, while ensembles of cortical neurons are proposed to form increasingly strong connections that store and represent remote memories as consolidation proceeds. Investigations into memory representations highlight discrepancies between the involvement of a cortical region in remote memory processes, the anterior cingulate cortex (ACC), and the hippocampus. The present thesis introduces a novel behavioural procedure that examines the ef- fect of increased processing demands on the hippocampus and the consequent effect on memory consolidation, storage and retrieval. Rats were trained on a single spatial task, two different spatial tasks, or one spatial and one non-spatial task. Regional involvement of the hippocampus and the ACC during retrieval were examined using immediate early genes and proteins of interest. Structural modifications in memory storage were examined using the Golgi-Cox method and quantification of dendritic complexity was an- alyzed through neuron reconstruction. The contribution of the ACC to spatial memory retrieval was assessed through behavioural performance and transient ACC pharmacological inactivation. The present thesis provides evidence that increased demand on the hip- pocampus results in accelerated processing of spatial memories. Findings show that the involvement of the ACC in memory processing can be manipulated by increasing hippocampal-processing demand. Functional, structural and be- havioral data suggest that taxing the demand on the hippocampus accelerates the involvement of the ACC. There is also evidence of continued hippocampal involvement in memory processes at recent and remote time points. Taken to- gether, these findings indicate an increased recruitment of the ACC, but not an accelerated independence from the hippocampus, in spatial memory processes. The use of a novel behavioral procedure aimed at increasing hippocampal- demand can reveal processes more similar to those present in the human con- dition, where there is a constant demand on memory systems. The novelty of the findings presented in this thesis will further our understanding of remote memory.