School of Physiology and Pharmacology, University of Bristol, Bristol, BS8 1TD United Kingdom, and Eli Lilly and Company, Windlesham, Surrey, GU20 6PH United Kingdom.
J Neurosci. 2013 Nov 20;33(47):18469-80. doi: 10.1523/JNEUROSCI.2197-13.2013.
The 8-15 Hz thalamocortical oscillations known as sleep spindles are a universal feature of mammalian non-REM sleep, during which they are presumed to shape activity-dependent plasticity in neocortical networks. The cortex is hypothesized to contribute to initiation and termination of spindles, but the mechanisms by which it implements these roles are unknown. We used dual-site local field potential and multiple single-unit recordings in the thalamic reticular nucleus (TRN) and medial prefrontal cortex (mPFC) of freely behaving rats at rest to investigate thalamocortical network dynamics during natural sleep spindles. During each spindle epoch, oscillatory activity in mPFC and TRN increased in frequency from onset to offset, accompanied by a consistent phase precession of TRN spike times relative to the cortical oscillation. In mPFC, the firing probability of putative pyramidal cells was highest at spindle initiation and termination times. We thus identified "early" and "late" cell subpopulations and found that they had distinct properties: early cells generally fired in synchrony with TRN spikes, whereas late cells fired in antiphase to TRN activity and also had higher firing rates than early cells. The accelerating and highly structured temporal pattern of thalamocortical network activity over the course of spindles therefore reflects the engagement of distinct subnetworks at specific times across spindle epochs. We propose that early cortical cells serve a synchronizing role in the initiation and propagation of spindle activity, whereas the subsequent recruitment of late cells actively antagonizes the thalamic spindle generator by providing asynchronous feedback.
被称为睡眠纺锤波的 8-15 Hz 丘脑皮层振荡是哺乳动物非快速眼动睡眠的普遍特征,在非快速眼动睡眠期间,它们被认为可以塑造新皮层网络中的活动依赖性可塑性。皮层被假设为启动和终止纺锤波的作用,但它实现这些作用的机制尚不清楚。我们在休息时使用自由活动大鼠的丘脑网状核 (TRN) 和内侧前额叶皮层 (mPFC) 的双位点局部场电位和多个单细胞记录,研究自然睡眠纺锤波期间的丘脑皮层网络动力学。在每个纺锤波时期,mPFC 和 TRN 的振荡活动从开始到结束频率增加,伴随着 TRN 尖峰时间相对于皮层振荡的一致相位超前。在 mPFC 中,假定的锥体神经元的发射概率在纺锤波开始和结束时最高。因此,我们确定了“早期”和“晚期”细胞亚群,并发现它们具有不同的特性:早期细胞通常与 TRN 尖峰同步发射,而晚期细胞与 TRN 活动反相发射,并且比早期细胞具有更高的发射率。因此,在纺锤波过程中,丘脑皮层网络活动的加速和高度结构化的时间模式反映了在特定时间在纺锤波时期内特定子网络的参与。我们提出,早期皮层细胞在纺锤波活动的启动和传播中起同步作用,而随后招募的晚期细胞通过提供异步反馈来积极拮抗丘脑纺锤波发生器。