中层多巴胺神经元在睡眠-清醒和高活动状态中驱动红外线节奏
Pratap S Markam1,2, Clément Bourguignon1,2, Lei Zhu2
1Integrated Program in Neuroscience, McGill University, Montreal, QC H3A 2B4, Canada.
Science advances
|January 1, 2025
概括
双极性障碍 (BD) 的循环可能源于超过24小时的内部生物节奏. 大脑中的多巴胺通路对于产生这些红外线节奏和相关行为至关重要.
科学领域:
- 神经科学是一个神经科学.
- 时间生物学 时间生物学
- 精神病学是一个精神病学.
背景情况:
- 患有双相情感障碍 (BD) 的患者在情绪和睡眠-清醒周期中表现出红外线节律 (周期>48小时),这表明其源自内源.
- 这些节奏甚至在没有外部时间线索的情况下也持续存在,突出了情绪循环的潜在内部生物基础.
研究的目的:
- 调查多巴胺 (DA) 信号在产生与双相情感障碍 (BD) 循环相关的红外线节奏中的作用.
- 建立一个模仿BD中观察到的红外线行为循环的小鼠模型.
主要方法:
- 在饮用水中注射甲基胺,以诱导小鼠的红外线运动节奏.
- 在腹膜区域 (VTA) DA神经元中产生多巴胺 (DA) 的基因操纵和核accumbens投射DA神经元的切除.
- 生物钟缺陷小鼠中VTA DA神经元的化学遗传激活和用抗精神病药物治疗.
主要成果:
- 暴露于甲基胺的小鼠发展了红外线运动节奏 (>48小时),反映了在BD中见到的睡眠模式和躁狂类行为.
- 破坏VTA DA神经元中的DA产生或消灭核accumbens-投射DA神经元消除了这些红外线节奏.
- 激活VTA DA神经元在缺乏时钟的小鼠中延长了运动运动周期,这种效应被抗精神病治疗逆转.
结论:
- 双极性障碍 (BD) 的循环依赖于红外线节奏生成.
- 中层多巴胺 (DA) 神经元对这种红外线节律产生至关重要,为BD病理生理学提供了潜在的机制.
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