First Author | Onishi T | Year | 2018 |
Journal | Sci Rep | Volume | 8 |
Issue | 1 | Pages | 1692 |
PubMed ID | 29374282 | Mgi Jnum | J:264495 |
Mgi Id | MGI:6148616 | Doi | 10.1038/s41598-018-20090-0 |
Citation | Onishi T, et al. (2018) The Altered Supramolecular Structure of Dopamine D2 Receptors in Disc1-deficient Mice. Sci Rep 8(1):1692 |
abstractText | Disc1 is a susceptibility gene for psychiatric disorders including schizophrenia. It has been suggested that excess transmission through dopamine type 2 receptors (D2Rs) in the striatum is an underlying mechanism of pathogenesis. In this study, we used super-resolution microscopy to study the distribution of D2Rs at the nanoscale in mice lacking exons 2 and 3 of Disc1 (Disc1-deficient mice). We found that D2Rs in the nucleus accumbens (NAc) of wild-type mice form nanoclusters (~ 20,000 nm(2)), and that Disc1-deficient mice have larger and more D2R nanoclusters than wild-type mice. Interestingly, administration of clozapine reduced the size and spatial distribution of the nanoclusters only in Disc1-deficient mice. Moreover, we observed that medium spiny neurons in the NAc of Disc1-deficient mice had reduced spine density on their dendrites than did wild-type mice, and this was also reversed by clozapine administration. The altered D2R nanoclusters might be morphological representations of the altered dopaminergic transmission in disease states such as schizophrenia. |