Dopamine is critical for the normal functioning of the basal ganglia, modulating both input and output nuclei of this system. The distribution and function of each of the five dopamine receptor subtypes have been studied extensively in the striatum. However, the role of extrastriatal dopamine receptors in basal ganglia information processing is less clear. Here, we studied the anatomical distribution of dopamine receptors in one of the output nuclei of the rodent basal ganglia, the entopeduncular nucleus (EP). The presence of all dopamine receptor subtypes was verified in the EP using immunostaining. We detected co-localization of dopamine receptors with VGAT, which suggests presynaptic expression on GABAergic terminals. D1R and D2R were strongly colocalized with VGAT, whereas DR3-5 showed only sparse co-localization. We further labeled striatal or pallidal neurons with GFP and showed that only D1 receptors were co-localized with striatal terminals, while only D2R and D3R were co-localized with pallidal terminals. Dopamine receptors were also strongly co-localized with MAP2, indicating postsynaptic expression. Overall, these findings suggest that the dopaminergic system modulates activity in the EP both directly via postsynaptic receptors, and indirectly via GABAergic synapses stemming from the direct and indirect pathways.
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The authors would like to thank Dr. Avi Jacob for his excellent assistance with confocal imaging and Ziv Almog for his excellent assistance with graphic design.
This work was supported by a Grant from the Israel Science Foundation—Heritage Biomedical Science Partnership program of the Israel Science Foundation to AK and IBG (#138/15), and the Paul Feder foundation for neurodegenerative disorder research Grant to EO.
Compliance with ethical standards
Conflict of interest
The authors declare they have no conflict of interest.
All experimental procedures were approved and supervised by the Institutional Animal Care and Use Committee and were in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and the Bar-Ilan University Guidelines for the Use and Care of Laboratory Animals in Research. This study was approved by the Israel National Committee for Experiments in Laboratory Animals at the Ministry of Health. This article does not contain any studies with human participants performed by any of the authors.
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