Repetitive and compulsive-like behaviors lead to cognitive dysfunction in Disc1Δ2-3/Δ2-3 mice

B. Wulaer, T. Nagai, A. Sobue, N. Itoh, K. Kuroda, K. Kaibuchi, Toshitaka Nabeshima, K. Yamada

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 (Disc1Δ2-3/Δ2-3 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. Disc1Δ2-3/Δ2-3 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 Disc1Δ2-3/Δ2-3 mice were significantly higher than those by WT mice, suggesting perseverative/compulsive behaviors by Disc1Δ2-3/Δ2-3 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 Disc1Δ2-3/Δ2-3 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 Disc1Δ2-3/Δ2-3 mice are associated with hyperactivity of the DMS.

Original languageEnglish
Article numbere12478
JournalGenes, Brain and Behavior
Volume17
Issue number8
DOIs
Publication statusPublished - 01-11-2018

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Compulsive Behavior
Calcium Carbonate
Schizophrenia
Cognitive Dysfunction
Clozapine
Reward
Cognition
Molecular Biology
Exons

All Science Journal Classification (ASJC) codes

  • Genetics
  • Neurology
  • Behavioral Neuroscience

Cite this

Wulaer, B., Nagai, T., Sobue, A., Itoh, N., Kuroda, K., Kaibuchi, K., ... Yamada, K. (2018). Repetitive and compulsive-like behaviors lead to cognitive dysfunction in Disc1Δ2-3/Δ2-3 mice. Genes, Brain and Behavior, 17(8), [e12478]. https://doi.org/10.1111/gbb.12478
Wulaer, B. ; Nagai, T. ; Sobue, A. ; Itoh, N. ; Kuroda, K. ; Kaibuchi, K. ; Nabeshima, Toshitaka ; Yamada, K. / Repetitive and compulsive-like behaviors lead to cognitive dysfunction in Disc1Δ2-3/Δ2-3 mice. In: Genes, Brain and Behavior. 2018 ; Vol. 17, No. 8.
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abstract = "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 (Disc1Δ2-3/Δ2-3 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. Disc1Δ2-3/Δ2-3 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 Disc1Δ2-3/Δ2-3 mice were significantly higher than those by WT mice, suggesting perseverative/compulsive behaviors by Disc1Δ2-3/Δ2-3 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 Disc1Δ2-3/Δ2-3 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 Disc1Δ2-3/Δ2-3 mice are associated with hyperactivity of the DMS.",
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Repetitive and compulsive-like behaviors lead to cognitive dysfunction in Disc1Δ2-3/Δ2-3 mice. / Wulaer, B.; Nagai, T.; Sobue, A.; Itoh, N.; Kuroda, K.; Kaibuchi, K.; Nabeshima, Toshitaka; Yamada, K.

In: Genes, Brain and Behavior, Vol. 17, No. 8, e12478, 01.11.2018.

Research output: Contribution to journalArticle

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