Olcese Umberto, Bos Jeroen J, Vinck Martin, Lankelma Jan V, van Mourik-Donga Laura B, Schlumm Friederike, Pennartz Cyriel M A
Cognitive and Systems Neuroscience Group, Swammerdam Institute for Life Sciences, University of Amsterdam, 1098XH Amsterdam, The Netherlands.
Cognitive and Systems Neuroscience Group, Swammerdam Institute for Life Sciences, University of Amsterdam, 1098XH Amsterdam, The Netherlands
J Neurosci. 2016 Jul 20;36(29):7676-92. doi: 10.1523/JNEUROSCI.4201-15.2016.
Behavioral states are commonly considered global phenomena with homogeneous neural determinants. However, recent studies indicate that behavioral states modulate spiking activity with neuron-level specificity as a function of brain area, neuronal subtype, and preceding history. Although functional connectivity also strongly depends on behavioral state at a mesoscopic level and is globally weaker in non-REM (NREM) sleep and anesthesia than wakefulness, it is unknown how neuronal communication is modulated at the cellular level. We hypothesize that, as for neuronal activity, the influence of behavioral states on neuronal coupling strongly depends on type, location, and preceding history of involved neurons. Here, we applied nonlinear, information-theoretical measures of functional connectivity to ensemble recordings with single-cell resolution to quantify neuronal communication in the neocortex and hippocampus of rats during wakefulness and sleep. Although functional connectivity (measured in terms of coordination between firing rate fluctuations) was globally stronger in wakefulness than in NREM sleep (with distinct traits for cortical and hippocampal areas), the drop observed during NREM sleep was mainly determined by a loss of inter-areal connectivity between excitatory neurons. Conversely, local (intra-area) connectivity and long-range (inter-areal) coupling between interneurons were preserved during NREM sleep. Furthermore, neuronal networks that were either modulated or not by a behavioral task remained segregated during quiet wakefulness and NREM sleep. These results show that the drop in functional connectivity during wake-sleep transitions globally holds true at the cellular level, but confine this change mainly to long-range coupling between excitatory neurons.
Studies performed at a mesoscopic level of analysis have shown that communication between cortical areas is disrupted in non-REM sleep and anesthesia. However, the neuronal determinants of this phenomenon are not known. Here, we applied nonlinear, information-theoretical measures of functional coupling to multi-area tetrode recordings from freely moving rats to investigate whether and how brain state modulates coordination between individual neurons. We found that the previously observed drop in functional connectivity during non-REM (NREM) sleep can be explained by a decrease in coupling between excitatory neurons located in distinct brain areas. Conversely, intra-area communication and coupling between interneurons are preserved. Our results provide significant new insights into the neuron-level mechanisms responsible for the loss of consciousness occurring in NREM sleep.
行为状态通常被视为具有同质神经决定因素的全局现象。然而，最近的研究表明，行为状态根据脑区、神经元亚型和先前历史，以神经元水平的特异性调节放电活动。尽管功能连接性在介观水平上也强烈依赖于行为状态，并且在非快速眼动（NREM）睡眠和麻醉状态下整体上比清醒时弱，但尚不清楚在细胞水平上神经元通讯是如何被调节的。我们假设，至于神经元活动，行为状态对神经元耦合的影响强烈依赖于所涉及神经元的类型、位置和先前历史。在这里，我们将功能连接性的非线性、信息理论测量方法应用于具有单细胞分辨率的整体记录，以量化大鼠在清醒和睡眠期间新皮层和海马体中的神经元通讯。尽管功能连接性（以放电率波动之间的协调性来衡量）在清醒时整体上比在NREM睡眠时更强（皮层和海马体区域有不同特征），但在NREM睡眠期间观察到的下降主要是由兴奋性神经元之间区域间连接性的丧失所决定的。相反，中间神经元之间的局部（区域内）连接性和长程（区域间）耦合在NREM睡眠期间得以保留。此外，在安静清醒和NREM睡眠期间，受行为任务调节或未受调节的神经元网络仍然是分离的。这些结果表明，清醒 - 睡眠转换期间功能连接性的下降在细胞水平上整体上是成立的，但这种变化主要局限于兴奋性神经元之间的长程耦合。
在介观分析水平上进行的研究表明，在非快速眼动睡眠和麻醉状态下，皮层区域之间的通讯会被破坏。然而，这种现象的神经元决定因素尚不清楚。在这里，我们将功能耦合的非线性、信息理论测量方法应用于自由活动大鼠的多区域四极记录，以研究脑状态是否以及如何调节单个神经元之间的协调性。我们发现，先前观察到在非快速眼动（NREM）睡眠期间功能连接性的下降可以通过位于不同脑区的兴奋性神经元之间耦合的减少来解释。相反，区域内通讯和中间神经元之间的耦合得以保留。我们的结果为非快速眼动睡眠中发生的意识丧失所涉及的神经元水平机制提供了重要的新见解。
