Sleep-Dependent Reactivation of Ensembles in Motor Cortex Promotes Skill Consolidation.
Sleep-Dependent Reactivation of Ensembles in Motor Cortex Promotes Skill Consolidation.
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DOI：
10.1371/journal.pbio.1002263
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发表时间：
2015
期刊：
影响因子：
9.8
通讯作者：
Ganguly K
中科院分区：
文献类型：
--
作者：
Ramanathan DS;Gulati T;Ganguly K
尽管之前的许多研究表明，睡眠后运动技能会获得离线行为，但其潜在的神经机制仍然知之甚少。为了研究离线收益的神经生理学基础，我们在大鼠学习熟练的上肢任务时，在运动皮质进行了单单位记录。我们发现，睡眠在保持准确性的同时提高了运动速度。这些线下改善与非快速眼动(NREM)睡眠期间任务相关集合的重播以及将运动皮质集合与运动更紧密地捆绑在一起的时间转移有关；这种离线收益和时间转移在睡眠限制下并不明显。有趣的是，重播与慢波事件和纺锤波活动爆发的巧合有关。经历最一致回放的神经元也经历了最显著的时间移位和与运动任务的绑定。值得注意的是，只有当动物第一次学习这项技能时，才会出现重演和睡眠后相关的表现改善；在学习的后期阶段(即运动运动学稳定后)继续练习并没有显示重演的证据。我们的结果强调了睡眠中同步神经活动的重播如何在早期运动学习中调节大规模神经可塑性和稳定运动学。在大鼠的非快速眼动睡眠中，最近学到的运动技能的巩固和离线改进与任务相关神经集合的同步重新激活有关。睡眠已被证明有助于巩固习得的运动任务。换句话说，即使在没有进一步训练的情况下，睡眠也可以在一项新的运动技能上诱导“离线”增长。然而，睡眠是如何引起这种变化的还没有明确的认识。一种假设是，睡眠期间记忆的巩固是通过学习过程中参与的神经元的重新激活来实现的。在这项研究中，我们通过记录大鼠在学习一项新的运动技能时以及在训练前后的睡眠中运动皮质中神经元的数量来检验这一假设。我们发现，在学习过程中，任务相关神经元的子集形成了高度同步的集合。有趣的是，在随后的睡眠区块中，这些相同的神经集合被重新激活，重新激活的程度与运动记忆巩固的几个指标相关。具体地说，在睡眠后，动物在保持精确度的同时执行任务的速度加快了，神经元组装的活动与运动动作更紧密地联系在一起。进一步的分析表明，重新激活事件是间歇性的，并与纺锤波一起发生--纺锤波是睡眠期间常见的大脑活动突发。这一观察结果与之前在人类身上的发现一致，即纺锤波与习得任务的巩固相关。因此，我们的研究为支持睡眠中运动记忆巩固的神经网络机制提供了洞察力，并可能导致新的干预措施，可以增强健康和受损神经系统的技能学习。
Despite many prior studies demonstrating offline behavioral gains in motor skills after sleep, the underlying neural mechanisms remain poorly understood. To investigate the neurophysiological basis for offline gains, we performed single-unit recordings in motor cortex as rats learned a skilled upper-limb task. We found that sleep improved movement speed with preservation of accuracy. These offline improvements were linked to both replay of task-related ensembles during non-rapid eye movement (NREM) sleep and temporal shifts that more tightly bound motor cortical ensembles to movements; such offline gains and temporal shifts were not evident with sleep restriction. Interestingly, replay was linked to the coincidence of slow-wave events and bursts of spindle activity. Neurons that experienced the most consistent replay also underwent the most significant temporal shift and binding to the motor task. Significantly, replay and the associated performance gains after sleep only occurred when animals first learned the skill; continued practice during later stages of learning (i.e., after motor kinematics had stabilized) did not show evidence of replay. Our results highlight how replay of synchronous neural activity during sleep mediates large-scale neural plasticity and stabilizes kinematics during early motor learning. During non-REM sleep in rats, consolidation and offline improvements of a recently learned motor skill are linked to synchronous reactivation of task-related neural ensembles. Sleep has been shown to help in consolidating learned motor tasks. In other words, sleep can induce “offline” gains in a new motor skill even in the absence of further training. However, how sleep induces this change has not been clearly identified. One hypothesis is that consolidation of memories during sleep occurs by “reactivation” of neurons engaged during learning. In this study, we tested this hypothesis by recording populations of neurons in the motor cortex of rats while they learned a new motor skill and during sleep both before and after the training session. We found that subsets of task-relevant neurons formed highly synchronized ensembles during learning. Interestingly, these same neural ensembles were reactivated during subsequent sleep blocks, and the degree of reactivation was correlated with several metrics of motor memory consolidation. Specifically, after sleep, the speed at which animals performed the task while maintaining accuracy was increased, and the activity of the neuronal assembles were more tightly bound to motor action. Further analyses showed that reactivation events occurred episodically and in conjunction with spindle-oscillations—common bursts of brain activity seen during sleep. This observation is consistent with previous findings in humans that spindle-oscillations correlate with consolidation of learned tasks. Our study thus provides insight into the neuronal network mechanism supporting consolidation of motor memory during sleep and may lead to novel interventions that can enhance skill learning in both healthy and injured nervous systems.