This thesis explores the influence of brain regions in the extended hippocampal system on the activity of the retrosplenial cortex in the rat. The primary motivation of the experiments presented in this thesis is to improve the understanding of the vulnerability of the retrosplenial cortex, especially in the context of diencephalic amnesia and Alzheimer's disease. Using molecular imaging, it is shown that discernible networks of brain regions are active even at different training levels of the same spatial memory task, not just between different tasks. I provide evidence that multiple brain regions exhibit a relationship with memory. Importantly, these regions display associations with different memory components, which change according to the experience and the performance level of the subjects. The lesion studies provide information about the vulnerability of granular b retrosplenial cortex to distal damage in certain regions. The pattern of the terminations of the projections from each region to the retrosplenial cortex does not appear to be predictive of the impact that damage to each will have on immediate-early gene activity in the latter. In addition to the anterior thalamic nuclei, the retrosplenial cortex is vulnerable to damage in the entorhinal cortex and in the hippocampus, but not in the laterodorsal thalamic nucleus. I show that retrosplenial cortex dysfunction can occur as early as one week after anterior thalamic nuclei lesions. Evidence is also shown to suggest that both granular and dysgranular subregions of the retrosplenial cortex are affected as a result of anterior thalamic nuclei lesions. Finally, the presence of hormonal alterations in dysfunctional retrosplenial cortex tissue and evidence from a microarray analysis suggest that this region exhibits widespread alterations in cellular function after anterior thalamic nuclei lesions. The effects presented and the mechanisms that are proposed contribute to our understanding of the vulnerability of the retrosplenial cortex to neurological insults.