| First Author | Wulaer B | Year | 2018 |
| Journal | Genes Brain Behav | Volume | 17 |
| Issue | 8 | Pages | e12478 |
| PubMed ID | 29635888 | Mgi Jnum | J:276635 |
| Mgi Id | MGI:6317291 | Doi | 10.1111/gbb.12478 |
| Citation | Wulaer B, et al. (2018) Repetitive and compulsive-like behaviors lead to cognitive dysfunction in Disc1(Delta2-3/Delta2-3) mice. Genes Brain Behav 17(8):e12478 |
| abstractText | Disrupted-in-schizophrenia 1 (Disc1) is a key molecular driver for the biology of mental diseases. In order to investigate its role in brain function, we previously generated mice lacking exons 2 and 3 of Disc1 on a C57BL/6J genetic background (Disc1(Delta2-3/Delta2-3) mice), which have a deficiency of the full-length Disc1 protein. In the present study, we examined the role of Disc1 in cognitive function using a touchscreen-based visual discrimination (VD) task in which mice had to discriminate 1 of 2 stimuli simultaneously displayed on the screen and received a liquid reward. Disc1(Delta2-3/Delta2-3) mice showed impaired performance in the VD task, and this was mainly attributed to the perseverative response being significantly stronger than that in wild-type (WT) mice. Furthermore, the numbers of marbles buried in the marble burying test and nestlets shredded in the nestlet shredding test by Disc1(Delta2-3/Delta2-3) mice were significantly higher than those by WT mice, suggesting perseverative/compulsive behaviors by Disc1(Delta2-3/Delta2-3) mice. A treatment with clozapine ameliorated behavioral deficits in the VD and marble burying tasks. c-Fos expression was significantly stronger in the dorsomedial striatum (DMS), but not the dorsolateral striatum (DLS) after the first VD session in Disc1(Delta2-3/Delta2-3) mice than in WT mice. The treatment of mice that had previously expressed hM3Dq in the DMS with clozapine-N-oxide (CNO) impaired performance in the VD task. These results suggest that cognitive impairments accompanied by perseverative/compulsive behaviors in Disc1(Delta2-3/Delta2-3) mice are associated with hyperactivity of the DMS. |
