Functional recovery after stroke is associated with a remapping of neural circuits. This reorganization is often associated with low-frequency, high-amplitude oscillations in the peri-infarct zone in both rodents and humans. These oscillations are reminiscent of sleep slow waves (SW) and suggestive of a role for sleep in brain plasticity that occur during stroke recovery; however, direct evidence is missing. Using a stroke model in male mice, we showed that stroke was followed by a transient increase in NREM sleep accompanied by reduced amplitude and slope of ipsilateral NREM sleep SW. We next used 5 ms optical activation of Channelrhodopsin 2-expressing pyramidal neurons, or 200 ms silencing of Archeorhodopsin T-expressing pyramidal neurons, to generate local cortical UP, or DOWN, states, respectively, both sharing similarities with spontaneous NREM SW in freely moving mice. Importantly, we found that single optogenetically evoked SW (SW^opto) in the peri-infarct zone, randomly distributed during sleep, significantly improved fine motor movements of the limb corresponding to the sensorimotor stroke lesion site compared with spontaneous recovery and control conditions, while motor strength remained unchanged. In contrast, SW^opto during wakefulness had no effect. Furthermore, chronic SW^opto during sleep were associated with local axonal sprouting as revealed by the increase of anatomic presynaptic and postsynaptic markers in the peri-infarct zone and corresponding contralesional areas to cortical circuit reorganization during stroke recovery. These results support a role for sleep SW in cortical circuit plasticity and sensorimotor recovery after stroke and provide a clinically relevant framework for rehabilitation strategies using neuromodulation during sleep.

SIGNIFICANCE STATEMENT Brain stroke is one of the leading causes of death and major disabilities in the elderly worldwide. A better understanding of the pathophysiological mechanisms underlying spontaneous brain plasticity after stroke, together with an optimization of rehabilitative strategies, are essential to improve stroke treatments. Here, we investigate the role of optogenetically induced sleep slow waves in an animal model of ischemic stroke and identify sleep as a window for poststroke intervention that promotes neuroplasticity and facilitates sensorimotor recovery.

中风后的功能恢复与神经回路的重新映射有关。这种重组通常与啮齿动物和人类的梗死周围区域的低频，高振幅振荡有关。这些振荡使人联想到睡眠慢波（SW），提示中风恢复期间睡眠在大脑可塑性中的作用。但是，缺少直接的证据。在雄性小鼠中使用中风模型，我们发现中风后NREM睡眠短暂增加，同侧NREM睡眠SW幅度和斜率降低。接下来，我们分别使用5毫秒光学激活表达Channelrhodopsin 2的锥体神经元或200毫秒沉默表达Archhooroppsin T的锥体神经元，分别产生局部皮质UP或DOWN状态。两者在自由移动的小鼠中与自发的NREM SW具有相似之处。重要的是，我们发现单个光遗传学诱发的SW（SW^光）在梗死周围区，在睡眠期间随机分布，显著改善对应于与自发恢复和对照条件相比，感觉运动行程病变部位肢体，精细的电机运动而电机强度保持不变。相反，唤醒时的SW ^opto无效。此外，慢性SW^光电卒中恢复过程中，梗死周围区域和相应对侧区域的解剖学突触前和突触后标志物的增加表明，睡眠期间与局部轴突发芽有关。这些结果支持睡眠SW在中风后皮质回路可塑性和感觉运动恢复中的作用，并为临床上在睡眠期间使用神经调节的康复策略提供相关的框架。

重要声明脑卒中是全球老年人死亡和严重残疾的主要原因之一。更好地了解卒中后自发性大脑可塑性的病理生理机制，以及优化康复策略，对于改善卒中治疗至关重要。在这里，我们研究了光遗传学诱导的睡眠慢波在缺血性中风的动物模型中的作用，并将睡眠确定为中风后干预的窗口，以促进神经可塑性并促进感觉运动恢复。