Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts 01609.
Illawarra Health and Medical Research Institute and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong 2522, Australia.
J Neurosci. 2021 Mar 3;41(9):1892-1907. doi: 10.1523/JNEUROSCI.1701-20.2020. Epub 2021 Jan 14.
Sleep, a state of quiescence associated with growth and restorative processes, is conserved across species. Invertebrates including the nematode exhibit sleep-like states during development, satiety, and stress. Here, we describe behavior and neural activity during sleep and awake states in adult hermaphrodites using new microfluidic methods. We observed effects of fluid flow, oxygen, feeding, odors, and genetic perturbations on long-term sleep behavior over 12 h. We developed a closed-loop sleep detection system to automatically deliver chemical stimuli to assess sleep-dependent changes to evoked neural responses in individual animals. Sleep increased the arousal threshold to aversive stimulation, yet the associated sensory neuron and first-layer interneuron responses were unchanged. This localizes adult sleep-dependent neuromodulation within interneurons presynaptic to the premotor interneurons, rather than afferent sensory circuits. However, sleep prolonged responses in appetitive chemosensory neurons, suggesting that sleep modulates responsiveness specifically across sensory systems rather than broadly damping global circuit activity. Much is known about molecular mechanisms that facilitate sleep control. However, it is unclear how these pathways modulate neural circuit-level sensory processing or how misregulation of neural activity contributes to sleep disorders. The nematode provides the ability to study neural circuitry with single-neuron resolution, and recent studies examined sleep states between developmental stages and when stressed. Here, we examine an additional form of spontaneous sleep in adult at the behavioral and neural activity levels. Using a closed-loop system, we show that delayed behavioral responses to aversive chemical stimulation during sleep arise from sleep-dependent sensorimotor modulation localized presynaptic to the premotor circuit, rather than early sensory circuits.
睡眠是一种与生长和修复过程相关的静止状态，在物种间是保守的。包括线虫在内的无脊椎动物在发育、饱食和应激期间表现出类似睡眠的状态。在这里，我们使用新的微流控方法描述了成年雌雄同体中的睡眠和清醒状态下的行为和神经活动。我们观察了流体流动、氧气、进食、气味和遗传扰动对 12 小时内长期睡眠行为的影响。我们开发了一种闭环睡眠检测系统，自动输送化学刺激物，以评估个体动物睡眠依赖性对诱发神经反应的变化。睡眠增加了对厌恶刺激的觉醒阈值，但相关的感觉神经元和第一层中间神经元的反应没有变化。这将成年动物睡眠依赖性神经调制定位在运动前中间神经元的突触前中间神经元内，而不是传入感觉回路。然而，睡眠延长了食欲性化学感觉神经元的反应，这表明睡眠专门调节感觉系统的反应能力，而不是广泛抑制全局电路活动。人们对促进睡眠控制的分子机制有了很多了解。然而，目前尚不清楚这些途径如何调节神经回路水平的感觉处理，或者神经活动的失调如何导致睡眠障碍。线虫提供了以单个神经元分辨率研究神经回路的能力，最近的研究检查了发育阶段之间和受到压力时的睡眠状态。在这里，我们在行为和神经活动水平上检查成年线虫的另一种自发睡眠形式。使用闭环系统，我们表明，睡眠期间对厌恶化学刺激的延迟行为反应源自睡眠依赖性感觉运动调制，该调制定位于运动前回路的突触前，而不是早期感觉回路。
