The role of the dentate gyrus in the formation of cognitive maps: Insights from Pavlovian fear conditioning in genetically modified mice

Animals generate complex internal representations of the outside world that they use to control and guide behavior. In Pavlovian Fear Conditioning this phenomenon is most evident in contextual fear conditioning. In this dissertation I conducted a systematic analysis of context fear conditioning using a number of genetically modified mice with a focus on manipulations of the dentate gyrus. The results indicate that decreasing tonic inhibition via genetic deletion of the alpha4 GABAAR results in enhanced hippocampus-dependent learning and memory and a paradoxical increased sensitivity to the learning impairments induced by ethanol. The dentate gyrus continually generates new neurons throughout post-natal life. Complete loss of this post-natal neurogenesis in DNMT1 conditional knock-out mice was associated with a specific deficit in incidental learning and an enhancement in contextual fear discrimination. Overall these findings argue that the dentate gyrus plays a critical role in the formation of hippocampus-dependent cognitive maps.