延长觉醒对运动性学习中前额叶皮层-小脑振荡同步化的影响及机制研究

Prolonged wakefulness (e.g. insomnia and sleep deprivation), which is commonplace in modern culture, often leads to the impairment in motor learning. However, the underlying mechanisms remain unclear. It has been suggested that both the prefrontal cortex (mPFC) and the cerebellum are critical for motor learning. Moreover, theta-band synchronization between the mPFC and the cerebellum contributes to the neurotransmission of motor command and the occurrence of motor learning. Because the neuronal activities in both areas are strongly influenced by the wakefulness- promoting systems and are sensitive to the prolonged wakefulness, our present project aims to investigate the change of oscillation synchronization between the mPFC and the cerebellum during the prolonged wakefulness. Additionally, the relationship between synchronization change and motor learning will be explored. To this end, several techniques are utilized, including the patch clamp recording, multiple units recording, optogenetics, behavioral tests, and so on. Then, we will explore the mechanisms underlying the change of oscillation synchronization, and will observe whether the abnormal synchronization and impaired motor learning can be reversed by functional potentiation of the wakefulness-promoting system under the prolonged wakefulness conditions. The outcomes from this project will provide new insights into relieving the impaired motor learning induced by the prolonged wakefulness.

以失眠和睡眠剥夺为代表的觉醒延长是现代社会的常见现象。在延长觉醒状态下人们常会出现运动性学习能力的下降，但相关机制仍不清楚。前额叶皮层和小脑是参与运动性学习的关键脑区，它们之间theta频带振荡同步化是运动意图信息传递和运动性学习发生的基础。由于二者神经元兴奋活动均受到促觉醒系统的调控，并对延长觉醒尤为敏感，因此本项目拟选择前额叶皮层-小脑通路振荡同步化为研究对象，采用在体电生理、光遗传学、微透析以及整体行为学等技术，研究在延长觉醒过程中前额叶皮层-小脑振荡同步化的变化规律，及其与运动性学习能力下降的相关性。在此基础上，初步探讨振荡同步化发生变化的机制，并观察在延长觉醒条件下增强特定促觉醒系统活动是否能够逆转振荡同步化和运动性学习行为的变化，以期为缓解延长觉醒引起的运动性学习功能减退症状提供新的思路。

以失眠和睡眠剥夺为代表的觉醒延长是现代社会的常见现象。在延长觉醒状态下人们常会出现运动性学习能力的下降，但相关机制仍不清楚。前额叶皮层和小脑是参与运动性学习的关键脑区，它们之间theta频带振荡同步化是运动意图信息传递和运动性学习发生的基础。由于二者神经元兴奋活动均受到促觉醒系统的调控，并对延长觉醒尤为敏感，因此本项目拟选择前额叶皮层-小脑通路振荡同步化为研究对象，以痕迹性眨眼条件反射为行为模型，采用在体电生理、光遗传学以及整体行为学等技术，研究在延长觉醒过程中前额叶皮层-小脑振荡同步化的变化规律，及其与运动性学习能力下降的相关性。在此基础上，初步探讨振荡同步化发生变化的机制，并观察在延长觉醒条件下是振荡同步化受到干扰并影响到运动性学习行为。我们的结果显示：（1）联合型运动学习过程中内侧前额叶皮层和小脑之间存在显著的theta频带（5-12Hz）振荡同步化。这种内侧前额叶皮层-小脑theta振荡同步化有助于提升动物以痕迹性眨眼条件反射为代表的运动学习行为表现的精确性。而干扰参与下丘脑orexin内源性促觉醒功能，将显著降低前额叶皮层-小脑theta振荡同步化水平，并会伴随有痕迹性眨眼条件反应的行为表现异常。（2）干扰动物训练后的睡眠可以阻碍动物痕迹性眨眼条件反射的记忆巩固。综上，本项目创新性地提出了“延长觉醒后前额叶皮层-小脑 theta 振荡同步化活动异常可能是运动性学习能力下降的机制”，这为改善延长觉醒所引起的运动性学习能力缺陷提供新的理论依据。