Distinct roles for primate caudate dopamine D1 and D2 receptors in visual discrimination learning revealed using shRNA knockdown.
The striatum plays important motor, associative and cognitive roles in brain functions. However, the rodent dorsolateral (the primate putamen) and dorsomedial (the primate caudate nucleus) striatum are not anatomically separated, making it difficult to distinguish their functions. By contrast, anatomical separation exists between the caudate nucleus and putamen in primates. Here, we successfully decreased dopamine D1 receptor (D1R) or D2R mRNA expression levels selectively in the marmoset caudate using shRNA knockdown techniques, as determined using positron emission tomography imaging with specific D1R and D2R ligands and postmortem in situ hybridization analysis. We then conducted a voxel-based correlation analysis between binding potential values of PET imaging and visual discrimination learning task performance in these genetically modified marmosets to find a critical role for the caudate D2R but no apparent role for the caudate D1R. This latter finding challenges the current understanding of the mechanisms underlying D1R activation in the caudate.
RIKEN, Brain Science Institute, Saitama, Japan.
Masafumi
M
Takaji
Primate Research Institute, Kyoto University, Aichi, Japan.
Atsushi
A
Takemoto
RIKEN, Center for Life Science Technologies, Hyogo, Japan.
Chihiro
C
Yokoyama
RIKEN, Brain Science Institute, Saitama, Japan.
Akiya
A
Watakabe
Jichi Medical University, Tochigi, Japan.
Hiroaki
H
Mizukami
Jichi Medical University, Tochigi, Japan.
Keiya
K
Ozawa
RIKEN, Center for Life Science Technologies, Hyogo, Japan.
Hirotaka
H
Onoe
Primate Research Institute, Kyoto University, Aichi, Japan.
Katsuki
K
Nakamura
RIKEN, Brain Science Institute, Saitama, Japan.
Tetsuo
T
Yamamori
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D002144:Callithrix / Q000378:metabolism*; D002421:Caudate Nucleus / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000378:metabolism*; D004193:Discrimination Learning / Q000502:physiology*; D017404:In Situ Hybridization, Fluorescence; D008279:Magnetic Resonance Imaging; D049268:Positron-Emission Tomography; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D065853:Spatial Learning
D034741:RNA, Small Interfering; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2