下丘脑腹侧乳头体前核DAT阳性神经元对睡眠-觉醒的调控作用OA
Role of DAT-positive Neurons in the Ventral Premammillary Nucleus in Sleep-Wake Regulation
目的:探究下丘脑腹侧乳头体前核(the ventral premammilary nucleus,PMv)在睡眠-觉醒节律调控中的作用及机制.方法:通过在体多通道和EEG/EMG 同步记录,验证PMv 脑区与睡眠-觉醒的相关性;c-Fos 免疫荧光染色分析睡眠剥夺对 PMv 神经元活性的影响,明确 PMv 脑区参与睡眠向觉醒状态的转换;脑立体定位注射与免疫组化相结合的方法,进一步明确 PMv 脑区参与睡眠向觉醒状态转换的神经元亚型;通过光遗传学和化学遗传学验证 PMv 脑区对觉醒的调节作用.结果:PMv 神经元活性与睡眠-觉醒状态密切相关,在 165 个记录神经元中,32.73%为觉醒高活性神经元,且群体放电活性在觉醒状态下显著高于快速眼动(REM)及非快速眼动(NREM)睡眠状态(P＜0.0001);睡眠剥夺后 PMv 神经元 c-Fos 表达量显著高于对照组及睡眠剥夺恢复组(P＜0.01),提示其参与睡眠向觉醒的转换过程;睡眠剥夺后 PMv 脑区 c-Fos 阳性神经元中多巴胺转运体(dopamine transporter,DAT)神经元占比达(72.3±1.2)%,表明 DAT 阳性神经元是 PMv 脑区参与觉醒调控的关键神经元亚型;光遗传学激活PMvDAT神经元可显著促进小鼠从 NREM 睡眠向觉醒状态的转换(P＜0.0001);化学遗传学激活 PMvDAT神经元能显著增加小鼠觉醒状态的时长(P＜0.01).结论:PMv 脑区参与睡眠-觉醒状态的调控,DAT 阳性神经元促进 NREM睡眠向觉醒转换并增加觉醒时长.
Objective To explore the role and mechanism of the ventral premammillary nucleus(PMv)in the regulation of sleep-wake rhythms.Methods In vivo multi-channel recording combined with synchronous EEG/EMG recording was per-formed to verify the correlation between the PMv and sleep-wake states.c-Fos immunofluorescence staining was used to an-alyze changes in the activity of PMv neurons induced by sleep deprivation and to clarify the involvement of the PMv in the transition from sleep to wakefulness.Brain stereotactic injection and immunohistochemistry were employed to further identify the neuronal subtypes in the PMv responsible for this state transition.Optogenetics and chemogenetics were adopted to ana-lyze the modulatory effect of the PMv on wakefulness.Results The activity of PMv neurons was closely associated with sleep-wake states.Among the 165 recorded neurons,32.73%were highly active during wakefulness.The collective firing activi-ty of neurons in the wake state was higher than that in rapid eye movement(REM)and non-rapid eye movement(NREM)sleep(P＜0.0001).The expression of c-Fos in PMv neurons was elevated after sleep deprivation compared with the control group and the sleep deprivation recovery group(P＜0.01),indicating its involvement in the transition from sleep to wake-fulness.After sleep deprivation,dopamine transporter(DAT)accounted for(72.3±1.2)%of c-Fos-positive neurons in the PMv,suggesting that DAT-positive neurons are the key neuronal subtype mediating wakefulness in this brain region.Optogenetic activation of PMvDAT neurons facilitated the transition from NREM sleep to wakefulness in mice(P＜0.0001),and chemogenetic activation of these neurons prolonged the duration of wakefulness(P＜0.01).Conclusion The PMv in in-volved in the regulation of sleep-wake states,and DAT-positive neurons in this region promote the transition from NREM sleep to wakefulness and extend the duration of wakefulness.The PMv is involved in the regulation of the sleep-wake states.DAT+neurons promote the transition from NREM sleep to wakefulness and increase wakefulness duration.
柯奇周;赖鹏舒;孟文洁;于红
湖北医药学院 基础医学院,湖北 十堰 442000||湖北医药学院 脑与类脑十堰市重点实验室,湖北 十堰 442000湖北医药学院 基础医学院,湖北 十堰 442000湖北医药学院 基础医学院,湖北 十堰 442000湖北医药学院 基础医学院,湖北 十堰 442000||湖北医药学院 脑与类脑十堰市重点实验室,湖北 十堰 442000
下丘脑腹侧乳头体前核多巴胺转运体睡眠觉醒
Ventral premammillary nucleusDopamine transporterSleepWakefulness
《湖北医药学院学报》 2026 (3)
283-289,301,8
湖北省自然科学基金(2024AFB720)湖北医药学院人才启动金(2022QDJZR010)
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