Effects of Aging on Cortical Neural Dynamics and Local Sleep Homeostasis in Mice.
Effects of Aging on Cortical Neural Dynamics and Local Sleep Homeostasis in Mice.
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DOI：
10.1523/jneurosci.2513-17.2018
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发表时间：
2018-04-18
期刊：
影响因子：
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通讯作者：
Vyazovskiy VV
中科院分区：
文献类型：
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作者：
McKillop LE;Fisher SP;Cui N;Peirson SN;Foster RG;Wafford KA;Vyazovskiy VV
健康的老龄化与睡眠的显著影响有关，包括其每日数量和结构，以及特定的EEG振荡。这些变化的神经生理学基础和生物学意义都不清楚，关键的问题是，衰老是否与睡眠需求减少或产生充足睡眠的能力减弱有关。在这里，我们测试了一个假设，即衰老可能会影响局部皮层网络，破坏产生和维持睡眠振荡的能力，以及对睡眠不足的局部稳态反应。我们进行了慢性记录的皮质神经活动和局部场电位从运动皮层在年轻和老年雄性C57 BL/6 J小鼠，在自发觉醒和睡眠，以及在睡眠剥夺后的睡眠。在老年动物中，我们观察到非快速眼动睡眠局部场电位慢波及其相关神经元沉默（OFF）期的发病率增加，而状态依赖性皮质神经元放电的总体模式在年龄之间大致相似。此外，我们观察到，在局部皮层网络活动水平上对睡眠剥夺的反应不受年龄的影响。因此，我们的数据表明，局部皮质神经动力学和局部睡眠稳态机制，至少在运动皮质，在小鼠健康衰老过程中没有受损。这表明可能存在强大的保护或补偿机制，以维持神经元功能在整个生命周期中的稳定，抵消睡眠量和结构的整体变化。睡眠中年龄依赖性变化的生物学意义尚不清楚，但可能反映了睡眠需求减少或产生深度睡眠阶段的能力降低。由于衰老与皮质睡眠振荡的深刻破坏有关，并且由于睡眠需求反映在皮质活动的特定模式中，因此我们对年轻和老年小鼠在清醒，睡眠和睡眠剥夺后的皮质神经活动进行了慢性电生理记录。我们发现，在自发睡眠和睡眠剥夺后恢复睡眠期间，老年小鼠大脑皮层活动的所有主要特征基本上都完好无损，这表明在整体睡眠中与年龄相关的变化不太可能来自新皮层内局部网络动态的破坏。
Healthy aging is associated with marked effects on sleep, including its daily amount and architecture, as well as the specific EEG oscillations. Neither the neurophysiological underpinnings nor the biological significance of these changes are understood, and crucially the question remains whether aging is associated with reduced sleep need or a diminished capacity to generate sufficient sleep. Here we tested the hypothesis that aging may affect local cortical networks, disrupting the capacity to generate and sustain sleep oscillations, and with it the local homeostatic response to sleep loss. We performed chronic recordings of cortical neural activity and local field potentials from the motor cortex in young and older male C57BL/6J mice, during spontaneous waking and sleep, as well as during sleep after sleep deprivation. In older animals, we observed an increase in the incidence of non-rapid eye movement sleep local field potential slow waves and their associated neuronal silent (OFF) periods, whereas the overall pattern of state-dependent cortical neuronal firing was generally similar between ages. Furthermore, we observed that the response to sleep deprivation at the level of local cortical network activity was not affected by aging. Our data thus suggest that the local cortical neural dynamics and local sleep homeostatic mechanisms, at least in the motor cortex, are not impaired during healthy senescence in mice. This indicates that powerful protective or compensatory mechanisms may exist to maintain neuronal function stable across the life span, counteracting global changes in sleep amount and architecture. SIGNIFICANCE STATEMENT The biological significance of age-dependent changes in sleep is unknown but may reflect either a diminished sleep need or a reduced capacity to generate deep sleep stages. As aging has been linked to profound disruptions in cortical sleep oscillations and because sleep need is reflected in specific patterns of cortical activity, we performed chronic electrophysiological recordings of cortical neural activity during waking, sleep, and after sleep deprivation from young and older mice. We found that all main hallmarks of cortical activity during spontaneous sleep and recovery sleep after sleep deprivation were largely intact in older mice, suggesting that the well-described age-related changes in global sleep are unlikely to arise from a disruption of local network dynamics within the neocortex.