Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD, USA.
Department of Neuroscience, University of Virginia, Charlottesville, VA, USA.
Nat Neurosci. 2023 Oct;26(10):1739-1750. doi: 10.1038/s41593-023-01426-0. Epub 2023 Sep 11.
Oligodendrocytes, the myelinating cells of the central nervous system (CNS), are generated from oligodendrocyte precursor cells (OPCs) that express neurotransmitter receptors. However, the mechanisms that affect OPC activity in vivo and the physiological roles of neurotransmitter signaling in OPCs are unclear. In this study, we generated a transgenic mouse line that expresses membrane-anchored GCaMP6s in OPCs and used longitudinal two-photon microscopy to monitor OPC calcium (Ca) dynamics in the cerebral cortex. OPCs exhibit focal and transient Ca increases within their processes that are enhanced during locomotion-induced increases in arousal. The Ca transients occur independently of excitatory neuron activity, rapidly decline when OPCs differentiate and are inhibited by anesthesia, sedative agents or noradrenergic receptor antagonists. Conditional knockout of α1A adrenergic receptors in OPCs suppresses spontaneous and locomotion-induced Ca increases and reduces OPC proliferation. Our results demonstrate that OPCs are directly modulated by norepinephrine in vivo to enhance Ca dynamics and promote population homeostasis.
少突胶质细胞是中枢神经系统（CNS）的髓鞘形成细胞，由表达神经递质受体的少突胶质前体细胞（OPC）产生。然而，影响体内 OPC 活性的机制以及神经递质信号在 OPC 中的生理作用尚不清楚。在这项研究中，我们生成了一种转基因小鼠品系，该品系在 OPC 中表达膜锚定的 GCaMP6s，并使用纵向双光子显微镜监测大脑皮层中 OPC 的钙（Ca）动力学。OPC 在其突起内表现出局灶性和短暂性的 Ca 增加，这些增加在觉醒引起的运动增加时增强。Ca 瞬变独立于兴奋性神经元活动发生，当 OPC 分化时迅速下降，并被麻醉、镇静剂或去甲肾上腺素能受体拮抗剂抑制。在少突胶质细胞中条件性敲除α1A 肾上腺素能受体可抑制自发和运动诱导的 Ca 增加，并减少 OPC 增殖。我们的结果表明，体内去甲肾上腺素直接调节 OPC 以增强 Ca 动力学并促进群体平衡。
