Differential roles of the dopamine 1-class receptors, D1R and D5R, in hippocampal dependent memory

Abstract

Pharmacological and global KO studies have worked to elucidate the function of dopamine 1-class receptors (D1Rs and D5Rs) in hippocampal-dependent learning and memory. Yet, these manipulations are unable to restrict D1R from D5R activity within hippocampal subregions. We generated mice that lack D1Rs or D5Rs in dentate gyrus (DG) granule cells of the hippocampus. This allowed us to characterize the precise role of D1Rs and D5Rs in modulating c-Fos activity in the hippocampus and in Pavlovian fear conditioning. We demonstrate that DG D1R deletion, but not D5R deletion, increases DG granule cell baseline c-Fos activity, decreases DG and CA3 c-Fos activity in response to contextual exposure and to contextual fear conditioning, impairs contextual memory formation, and enhances generalization of the conditioned fear response.