Department of Pharmacology, State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
J Neurosci Res. 2021 Jun;99(6):1689-1703. doi: 10.1002/jnr.24828. Epub 2021 Mar 13.
The lateral hypothalamus (LH) plays a key role in the maintenance of cortical activation and wakefulness. In the LH, the two main neuronal cell populations consist of excitatory glutamatergic neurons and inhibitory GABAergic neurons. Recent studies have shown that inhibitory LH GABAergic neurons are wake-promoting. However, the mechanism by which excitatory LH glutamatergic neurons contribute to sleep-wake regulation remains unclear. Using fiber photometry in male mice, we demonstrated that LH glutamatergic neurons exhibited high activities during both wakefulness and rapid eye movement sleep. Chemogenetic activation of LH glutamatergic neurons induced an increase in wakefulness that lasted for 6 hr, whereas suppression of LH glutamatergic neuronal activity caused a reduction in wakefulness. Brief optogenetic activation of LH glutamatergic neurons induced an immediate transition from slow-wave sleep to wakefulness, and long-lasting optogenetic stimulation of these neurons maintained wakefulness. Moreover, we found that LH-locus coeruleus/parabrachial nucleus and LH-basal forebrain projections mediated the wake-promoting effects of LH glutamatergic neurons. Taken together, our data indicate that LH glutamatergic neurons are essential for the induction and maintenance of wakefulness. The results presented here may advance our understanding of the role of LH in the control of wakefulness.
外侧下丘脑 (LH) 在维持皮质激活和觉醒中起着关键作用。在 LH 中，两种主要的神经元细胞群包括兴奋性谷氨酸能神经元和抑制性 GABA 能神经元。最近的研究表明，抑制性 LH GABA 能神经元具有促进觉醒的作用。然而，兴奋性 LH 谷氨酸能神经元如何参与睡眠-觉醒调节的机制尚不清楚。我们使用雄性小鼠的光纤光度测定法证明，LH 谷氨酸能神经元在觉醒和快速眼动睡眠期间均表现出高活性。LH 谷氨酸能神经元的化学遗传激活诱导了长达 6 小时的觉醒增加，而抑制 LH 谷氨酸能神经元的活动则导致觉醒减少。LH 谷氨酸能神经元的短暂光遗传激活会立即引起从慢波睡眠到觉醒的转变，而对这些神经元的长时间光遗传刺激则维持觉醒。此外，我们发现 LH-蓝斑/臂旁核和 LH-基底前脑投射介导了 LH 谷氨酸能神经元的促醒作用。总之，我们的数据表明 LH 谷氨酸能神经元对于诱导和维持觉醒是必不可少的。本研究结果可能有助于我们理解 LH 在控制觉醒中的作用。
