睡眠是人和动物不可缺少的一项重要生理活动，觉醒作为睡眠结构的重要组成元素之一， 参与并调控睡眠活动过程。 尽管长期以来有人已经提出丘脑-皮层投射系统在觉醒调控中起重要作用，但这一假设遭到了反复挑战。针对这个具有争议的问题， 本研究通过采用了光遗传、光纤记录、 化学遗传、神经示踪等方法， 证明了一个不属于正中旁丘脑（ paramedian thalamus） 的尾外侧多感觉丘脑核团，即丘脑后板内核（ PIN） ， 以及 PIN 对颞联合皮层（ TEa）和外嗅皮层（ ECT）的投射在自然睡眠中的觉醒维持以及外界感觉刺激诱发的觉醒中有重要调控功能。 通过本研究可以发现， PIN 中的谷氨酸能神经元在清醒和快速眼动（ REM） 睡 眠 期 间 活 动 强 烈 ， 并 且 对 声 音 和 光 刺 激 均 表 现 出 时 锁 反 应（ time-locked responses） 。 激活 PIN 中的谷氨酸能神经元， 以及它们到TEa/ECT 的投射通路均可以快速可靠的诱发非快速眼动（ NREM） 睡眠到觉醒的转换，并且能激活麻醉状态下动物的皮层。 而抑制 PIN 中的谷氨酸能神经元， 或者他们到 TEa/ECT 的投射通路可以显著的降低自然睡眠中的清醒时间占比以及感觉刺激诱发的觉醒概率。 本研究结果表明 PIN 以及 PIN 到 TEa/ECT 的投射通路在内源性和外源性诱发的觉醒调控中均起重要作用，不仅为丘脑-皮层投射系统调控觉醒提供了直接的因果证据， 并更新了上行网状激活系统背侧通路中丘脑核团所涵盖的范围。 除此之外， 本研究结果可能对患有嗜睡症、深度或长期无意识状态的患者具有临床治疗指导意义。
Sleep is an indispensable physiological activity for humans and animals. As one of the important elements of sleep structure, arousal takes part in and regulates the sleep process. Although an essential role of the thalamocortical projection system in wakefulness control has been proposed for a long time, this hypothesis has been repeatedly challenged. To this controversial issue, by using optogenetics, fiber photometry, chemogenetics, and neural tracing, this study demonstrated that the posterior intralaminar thalamic nucleus (PIN), which is a multisensory thalamic region and not a part of paramedian thalamus, and its glutamatergic projections to the temporal association cortices (TEa/ECT) make critical contribution to both sensory-evoked awakenings and the maintenance of awake state. In this research, the results showed that glutamatergic neurons in the PIN were endogenously more active during wakefulness and rapid eye movement (REM) sleep, and demonstrated time-locked responses upon both tone and light onsets. The activation of these neurons or their projections to the TEa/ECT reliably induced non-rapid eye movement (NREM) sleep-to-wake transitions and activated the cortex under general anesthesia, while inactivation significantly reduced awakenings elicited by salient sensory stimuli and decreased wakefulness. In summary, these findings indicate that PIN and PIN-TEa/ECT pathway play an important role in endogenous and exogenous induced arousal, provided causal evidences for the controlling of wakefulness by the thalamocortical projection system, and suggested a revision of the dorsal pathway of the ARAS concept. In addition, these results might have clinical implications for treating patients suffering from deep and prolonged state of unconsciousness.
