| 配分額 *注記 |
5,070千円 (直接経費: 3,900千円、間接経費: 1,170千円)
2015年度: 1,040千円 (直接経費: 800千円、間接経費: 240千円)
2014年度: 1,560千円 (直接経費: 1,200千円、間接経費: 360千円)
2013年度: 2,470千円 (直接経費: 1,900千円、間接経費: 570千円)
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| 研究概要 |
During the last year, we clarified neuroanatomical location of dopamine D2 receptor (D2R) in maintaining wakefulness.
We designed short-hairpin RNA of D2R carried by adeno-associated virus (AAV) to knockdown D2R in caudate-putamen (CPU), core of nucleus accumbens (NAc core) and shell of NAc (shell). The locomotor activity bioassay was performed using the infra sensors. EEG recordings were performed and automatically scored off-line by 10-s epochs as wakefulness, non-rapid eye movement (non-REM, NREM), and REM sleep by SleepSign. In addition, we also designed the AAV carrying human D2R gene (AAV-hD2R) to focally rescue the D2R in D2R KO mice.
After knockdown of D2R in the NAc core, the mice showed decreased locomotor activity during both day and night periods under the basal conditions, compared to the control mice. For the sleep-wake profile, core D2R knockdown mice exhibited a significant decrease in wakefulness, with a concomitant increase in NREM and REM sleep. While the D2R were rescued, mice showed an increase in locomotor activity. In mice with knockdown of D2R in NAc shell in WT or rescue of D2R in the KO mice, there were no significant changes in locomotion and sleep-wake profiles.
After knockdown of D2R in the CPU, the mice exhibited decreased locomotor activity, whereas there were no significant changes in sleep-wake profiles.
In conclusion, D2R in the NAc core plays an essential role in the maintenance of wakefulness. However, D2R in the CPU is important in controlling movement whereas D2R in NAc shell does not mediate the arousal and locomotion.
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