Harding Edward C, Ba Wei, Zahir Reesha, Yu Xiao, Yustos Raquel, Hsieh Bryan, Lignos Leda, Vyssotski Alexei L, Merkle Florian T, Constandinou Timothy G, Franks Nicholas P, Wisden William
Department of Life Sciences, Imperial College London, London, United Kingdom.
Wellcome-MRC Institute of Metabolic Science and MRC Metabolic Diseases Unit, University of Cambridge, Cambridge, United Kingdom.
Front Neurosci. 2021 Oct 14;15:709825. doi: 10.3389/fnins.2021.709825. eCollection 2021.
When mice are exposed to external warmth, nitric oxide synthase (NOS1) neurons in the median and medial preoptic (MnPO/MPO) hypothalamus induce sleep and concomitant body cooling. However, how these neurons regulate baseline sleep and body temperature is unknown. Using calcium photometry, we show that NOS1 neurons in MnPO/MPO are predominantly NREM and REM active, especially at the boundary of wake to NREM transitions, and in the later parts of REM bouts, with lower activity during wakefulness. In addition to releasing nitric oxide, NOS1 neurons in MnPO/MPO can release GABA, glutamate and peptides. We expressed tetanus-toxin light-chain in MnPO/MPO NOS1 cells to reduce vesicular release of transmitters. This induced changes in sleep structure: over 24 h, mice had less NREM sleep in their dark (active) phase, and more NREM sleep in their light (sleep) phase. REM sleep episodes in the dark phase were longer, and there were fewer REM transitions between other vigilance states. REM sleep had less theta power. Mice with synaptically blocked MnPO/MPO NOS1 neurons were also warmer than control mice at the dark-light transition (ZT0), as well as during the dark phase siesta (ZT16-20), where there is usually a body temperature dip. Also, at this siesta point of cooled body temperature, mice usually have more NREM, but mice with synaptically blocked MnPO/MPO NOS1 cells showed reduced NREM sleep at this time. Overall, MnPO/MPO NOS1 neurons promote both NREM and REM sleep and contribute to chronically lowering body temperature, particularly at transitions where the mice normally enter NREM sleep.
当小鼠暴露于外部温暖环境时，下丘脑正中视前区和内侧视前区（MnPO/MPO）中的一氧化氮合酶（NOS1）神经元会诱导睡眠并伴随身体降温。然而，这些神经元如何调节基线睡眠和体温尚不清楚。通过钙成像技术，我们发现MnPO/MPO中的NOS1神经元在非快速眼动睡眠（NREM）和快速眼动睡眠（REM）期间主要处于活跃状态，尤其是在从清醒到NREM转换的边界以及REM睡眠期的后期，而在清醒时活动较低。除了释放一氧化氮外，MnPO/MPO中的NOS1神经元还可以释放γ-氨基丁酸（GABA）、谷氨酸和肽类。我们在MnPO/MPO NOS1细胞中表达破伤风毒素轻链，以减少神经递质的囊泡释放。这导致了睡眠结构的变化：在24小时内，小鼠在黑暗（活跃）期的NREM睡眠减少，而在光照（睡眠）期的NREM睡眠增多。黑暗期的REM睡眠发作时间更长，其他警觉状态之间的REM转换次数减少。REM睡眠的θ波功率降低。在明暗转换（ZT0）时，以及在黑暗期午睡（ZT16 - 20）期间（通常此时体温会下降），突触阻断MnPO/MPO NOS1神经元的小鼠也比对照小鼠体温更高。此外，在体温下降的午睡时间点，小鼠通常会有更多的NREM睡眠，但突触阻断MnPO/MPO NOS1细胞的小鼠此时NREM睡眠减少。总体而言，MnPO/MPO NOS1神经元促进NREM和REM睡眠，并有助于长期降低体温，特别是在小鼠通常进入NREM睡眠的转换阶段。
