Department of Neurobiology, Institute for Biological Research-Sinisa Stankovic, University of Belgrade, Despot Stefan Blvd. 142, 11 000, Belgrade, Serbia.
Sleep Breath. 2011 Jan;15(1):35-47. doi: 10.1007/s11325-010-0327-6. Epub 2010 Feb 6.
Sigma and theta frequency electroencephalogram (EEG) oscillations exhibit substantial and well-recognized shifts with transitions across sleep and wake states. We aimed in this study to test the changes in coupling between these characteristic oscillations of non-rapid-eye-movement (NREM)/rapid-eye-movement (REM) sleep within and between cortical and pontine EEGs following monoaminergic lesion, by using the Pearson's product-moment correlation coefficients.
Experiments were performed in 14 adult, male Sprague Dawley rats chronically instrumented for sleep recording. We lesioned the dorsal raphe nucleus axon terminals in four rats using PCA neurotoxin (p-chloroamphetamine; Sigma-Aldrich, MO) administered as two intraperitoneal (IP) injections (6 mg/kg) 24 h apart. Lesioning of locus coeruleus axon terminals was performed in five rats using DSP-4 neurotoxin (N-2-chloroethyl-N-ethyl-2-bromobenzilamine; Sigma-Aldrich, MO) in a single IP dose of 50 mg/kg.
RESULTS & CONCLUSIONS: Our previous study [Saponjic et al., Physiol Behav 90:1-10, 2007] demonstrated that these systemically induced monoaminergic lesions failed to produce significant changes in sleep/wake distribution from control conditions. The present study, by using spectral analysis and by examining the Pearson's correlation coefficients and their approximate probability density (APD) distribution profiles in control and lesion condition, demonstrates significant augmentation of the sigma/theta coupling strength, an inversion of cortical sigma/theta coupling direction and emergence of an additional sigma/theta coupling "mode" specific to the post-lesion state only within the cortex. By using the Pearson's correlation coefficients and their APD profiles, instead of classical sleep/wake distribution analysis, as a measure of direction and strength of sigma/theta coupling within and between cortex and pons, we were able to uncover the impact of a tonically decreased level of brain monoamines as altered strength and mode of coupling between sigma and theta oscillations. Specifically, a new mode of sigma/theta coupling emerged following lesion, which was specific to NREM sleep, suggests that loss of monoaminergic signaling interferes with NREM sleep consolidation. Our results also indicate an importance of monoamines in control of the sleep spindle and theta rhythm generators.
西格玛和θ频率脑电图（EEG）振荡表现出与睡眠和觉醒状态转变相关的大量且公认的变化。我们旨在通过使用皮尔逊积矩相关系数，在单胺能损伤后，测试非快速眼动（NREM）/快速眼动（REM）睡眠中这些特征性振荡在皮质和脑桥 EEG 内和之间的耦合变化。
实验在 14 只成年雄性 Sprague Dawley 大鼠中进行，这些大鼠长期接受睡眠记录仪器的植入。我们使用 PCA 神经毒素（对氯苯丙胺；Sigma-Aldrich，MO）对 4 只大鼠的背侧中缝核轴突末梢进行损伤，该毒素通过两次腹腔内（IP）注射（6mg/kg），间隔 24 小时。我们使用 DSP-4 神经毒素（N-2-氯乙基-N-乙基-2-溴苯甲胺；Sigma-Aldrich，MO）对 5 只大鼠的蓝斑核轴突末梢进行损伤，剂量为 50mg/kg，单次腹腔内给药。
我们之前的研究[Saponjic 等人，生理行为 90:1-10,2007]表明，这些系统性诱导的单胺能损伤不会导致睡眠/觉醒分布与对照条件相比发生显著变化。本研究通过使用频谱分析，并通过检查对照和损伤条件下的皮尔逊相关系数及其近似概率密度（APD）分布曲线，表明在损伤后状态下，仅在皮质内，西格玛/θ 耦合强度显著增强，皮质西格玛/θ 耦合方向反转，以及出现一种额外的西格玛/θ 耦合“模式”。通过使用皮尔逊相关系数及其 APD 分布曲线，而不是经典的睡眠/觉醒分布分析，作为衡量皮质内和皮质与脑桥之间西格玛/θ 耦合的方向和强度的指标，我们能够揭示作为耦合强度和模式改变的大脑单胺能水平的持续降低的影响，西格玛和θ 振荡之间。具体来说，损伤后出现了一种新的西格玛/θ 耦合模式，这种模式仅在 NREM 睡眠中出现，表明单胺能信号的丧失会干扰 NREM 睡眠的巩固。我们的结果还表明，单胺类物质在控制睡眠纺锤波和θ节律发生器方面具有重要意义。
