Subcellular Localization of Dopamine D1 and D2 Receptors in the Mouse Hippocampus

Dopamine signaling through dopamine 1 receptors (D1R) and dopamine 2 receptors (D2R) regulates hippocampal synaptic plasticity underlying learning and memory, yet their subcellular localization within the hippocampus is unknown. Here we performed electron microscopic immunocytochemistry to elucidate the distribution of D1R and D2R in subregions of the mouse hippocampus. In CA1 and CA3 stratum radiatum (SR), D1R- and D2R-immunoreactivity was found primarily on pyramidal cell dendritic spines and unmyelinated axons, and to a lesser extent in axon terminals and glia. In both regions, D1R-labeled terminals formed predominantly asymmetric (excitatory-type) synapses on dendritic spines, whereas D2R-labeled terminals formed mainly symmetric (inhibitory-type) synapses on pyramidal cell dendritic shafts. In the dentate gyrus (DG) hilus, D1R-labeling was almost exclusively found in unmyelinated axons and glia. D2R immunoreactivity in the hilus similarly was present in unmyelinated axons and glia but was also detected in dendritic spines originating from mossy cells and in terminals forming symmetric synapses. These findings indicate that dopamine receptors are positioned to influence excitatory and inhibitory signaling in the murine hippocampus. As D1R and D2R exert opposing effects on neuronal signaling, their localization on pyramidal neuron compartments provides a structural substrate for bidirectional modulation of synaptic plasticity and pyramidal cell activity. In addition, the presence of D2Rs on inhibitory terminals contacting pyramidal neurons and hilar interneurons suggests a role in regulating inhibitory circuitry within the hippocampus.