Neural Computation Laboratory, Istituto Italiano di Tecnologia, 38068 Rovereto, Italy.
Center for Mind/Brain Sciences, University of Trento, 38068 Rovereto, Italy.
Proc Natl Acad Sci U S A. 2022 May 3;119(18):e2116507119. doi: 10.1073/pnas.2116507119. Epub 2022 Apr 29.
The noradrenergic locus coeruleus (LC) is a controller of brain and behavioral states. Activating LC neurons en masse by electrical or optogenetic stimulation promotes a stereotypical “activated” cortical state of high-frequency oscillations. However, it has been recently reported that spontaneous activity of LC cell pairs has sparse yet structured time-averaged cross-correlations, which is unlike the highly synchronous neuronal activity evoked by stimulation. Therefore, LC population activity could consist of distinct multicell ensembles each with unique temporal evolution of activity. We used nonnegative matrix factorization (NMF) to analyze large populations of simultaneously recorded LC single units in the rat LC. NMF identified ensembles of spontaneously coactive LC neurons and their activation time courses. Since LC neurons selectively project to specific forebrain regions, we hypothesized that distinct ensembles activate during different cortical states. To test this hypothesis, we calculated band-limited power and spectrograms of local field potentials in cortical area 24a aligned to spontaneous activations of distinct LC ensembles. A diversity of state modulations occurred around activation of different LC ensembles, including a typical activated state with increased high-frequency power as well as other states including decreased high-frequency power. Thus—in contrast to the stereotypical activated brain state evoked by en masse LC stimulation—spontaneous activation of distinct LC ensembles is associated with a multitude of cortical states.
蓝斑核（LC）的去甲肾上腺素能神经元是大脑和行为状态的控制器。通过电或光遗传学刺激大规模激活 LC 神经元会促进高频振荡的典型“激活”皮质状态。然而，最近有报道称，LC 细胞对的自发活动具有稀疏但结构均匀的时间平均互相关，这与刺激引起的高度同步神经元活动不同。因此，LC 群体活动可能由具有独特活动时间演化的不同多细胞集合体组成。我们使用非负矩阵分解 (NMF) 分析了大鼠 LC 中同时记录的大量 LC 单个单元。NMF 确定了自发共激活 LC 神经元及其激活时间过程的集合体。由于 LC 神经元选择性投射到特定的前脑区域，我们假设不同的集合体在不同的皮质状态下激活。为了验证这一假设，我们计算了与不同 LC 集合体自发激活对齐的皮质区 24a 中的局部场电位的带限功率和频谱图。在不同 LC 集合体激活时发生了多种状态调制，包括高频功率增加的典型激活状态以及其他状态，包括高频功率降低。因此——与大规模 LC 刺激引起的典型激活大脑状态相反——不同 LC 集合体的自发激活与多种皮质状态相关。
