Nat Commun:发现伏隔核调控觉醒的神经环路 为临床治疗伏隔核功能紊乱相关精神疾病提供新思路

2018-04-21 徐昕红 复旦大学基础医学院

近日,复旦大学基础医学院黄志力课题组发现,伏隔核多巴胺D1受体阳性神经元及其神经环路在觉醒调控中发挥重要作用,该作用机制的研究可为临床治疗伏隔核功能紊乱相关精神疾病提供新思路。4月20日,相关研究成果以《Nucleus accumbens controls wakefulness by a subpopulation of neurons expressing dopamine D1 recept

近日,复旦大学基础医学院黄志力课题组发现,伏隔核多巴胺D1受体阳性神经元及其神经环路在觉醒调控中发挥重要作用,该作用机制的研究可为临床治疗伏隔核功能紊乱相关精神疾病提供新思路。4月20日,相关研究成果以《Nucleus accumbens controls wakefulness by a subpopulation of neurons expressing dopamine D1 receptors》为题在线发表于《自然·通讯》。

为何人专注做事时能够长时间维持觉醒,但在无聊时却容易犯困?这一普遍现象引起了研究人员的思考。黄志力课题组长期关注脑内奖赏系统调控睡眠-觉醒作用及机制,发现与动机和快感相关的伏隔核(Nucleus accumbens,NAc)中D2/A2A受体阳性神经元调控睡眠,解释了动机行为缺乏性睡眠的神经调控机制(Nature Communications,2017)。另一方面,伏隔核是脑内的快乐中枢,在大脑的奖赏、快乐、笑、成瘾、侵犯、恐惧等活动中起重要作用,这些行为都依赖于机体的高度觉醒。但伏隔核内是否存在调控觉醒的神经元仍有待阐明。

研究人员利用转基因小鼠,通过在体光纤钙信号结合脑电记录,揭示伏隔核D1受体阳性神经元活性与觉醒高度相关。利用药理遗传学和光遗传学方法,发现特异性激活伏隔核D1受体阳性神经元可将小鼠从睡眠中唤醒,并延长清醒时间。反之,抑制这一类神经元活性动物表现为睡眠增加,并出现筑巢行为。通过病毒示踪、离体电生理等方法研究神经环路发现,伏隔核D1受体阳性神经元主要通过抑制中脑腹侧背盖区和外侧下丘脑中GABA能中间神经元,使多巴胺能神经元和食欲素神经元去抑制(活性增加),调控觉醒行为。

研究结果表明,伏隔核D1受体阳性神经元直接调控觉醒,构成了伏隔核执行运动、学习记忆、奖赏等高级行为的基础。作用机制的研究可能为临床治疗伏隔核功能紊乱相关精神疾病,如成瘾、精神分裂症的睡眠障碍提供新思路。



该项研究获得国家自然科学基金委面上及重点项目、创新群体和科技部973项目的支持。

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    2018-12-03 liye789132251
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    2018-05-20 guoyibin
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    2018-09-15 liuli5079
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    2019-02-25 晓辰
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    2018-04-23 衣带渐宽

    学习

    0

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    2018-04-21 哈哈869

    学了

    0