drd2-cre:ribotag mouse line unravels the possible diversity of dopamine d2 receptor-expressing cells of the dorsal mouse hippocampus

Hippocampus. 2015 Jul;25(7):858-75. doi: 10.1002/hipo.22408. Epub 2015 Feb 11.


Increasing evidences suggest that dopamine facilitates the encoding of novel memories by the hippocampus. However, the role of dopamine D2 receptors (D2R) in such regulations remains elusive due to the lack of the precise identification of hippocampal D2R-expressing cells. To address this issue, mice expressing the ribosomal protein Rpl22 tagged with the hemagglutinin (HA) epitope were crossed with Drd2-Cre mice allowing the selective expression of HA in D2R-containing cells (Drd2-Cre:RiboTag mice). This new transgenic model revealed a more widespread pattern of D2R-expressing cells identified by HA immunoreactivity than the one initially reported in Drd2-EGFP mice, in which the hilar mossy cells were the main neuronal population detectable. In Drd2-Cre:RiboTag mice, scattered HA/GAD67-positive neurons were detected throughout the CA1/CA3 subfields, being preferentially localized in stratum oriens and stratum lacunosum-moleculare. At the cellular level, HA-labeled cells located in CA1/CA3 subfields co-localized with calcium-binding proteins (parvalbumin, calbindin, and calretinin), neuropeptides (neuropeptide Y, somatostatin), and other markers (neuronal nitric oxide synthase, mGluR1α, reelin, coupTFII, and potassium channel-interacting protein 1). These results suggest that in addition to the glutamatergic hilar mossy cells, D2R-expressing cells constitute a subpopulation of GABAergic hippocampal interneurons.

Keywords: KChIP1; RiboTag mice; dopamine D2 receptor; hilar mossy cells; interneurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calbindin 2 / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Channelrhodopsins
  • Gene Expression Regulation / genetics*
  • Glutamate Decarboxylase / metabolism
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hippocampus / cytology*
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Confocal
  • Nerve Tissue Proteins / metabolism
  • Neurons / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism*
  • Reelin Protein
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism


  • Calbindin 2
  • Channelrhodopsins
  • DRD2 protein, mouse
  • Membrane Proteins
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • RPL22 protein, mouse
  • Receptors, Dopamine D2
  • Reelin Protein
  • Ribosomal Proteins
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Reln protein, mouse
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1