Haydon Philip G, Carmignoto Giorgio
Silvio Conte Center for Integration at the Tripartite Synapse, Department of Neuroscience, University of Pennsylvania School of Medicine, PA 19104, USA.
Physiol Rev. 2006 Jul;86(3):1009-31. doi: 10.1152/physrev.00049.2005.
From a structural perspective, the predominant glial cell of the central nervous system, the astrocyte, is positioned to regulate synaptic transmission and neurovascular coupling: the processes of one astrocyte contact tens of thousands of synapses, while other processes of the same cell form endfeet on capillaries and arterioles. The application of subcellular imaging of Ca2+ signaling to astrocytes now provides functional data to support this structural notion. Astrocytes express receptors for many neurotransmitters, and their activation leads to oscillations in internal Ca2+. These oscillations induce the accumulation of arachidonic acid and the release of the chemical transmitters glutamate, d-serine, and ATP. Ca2+ oscillations in astrocytic endfeet can control cerebral microcirculation through the arachidonic acid metabolites prostaglandin E2 and epoxyeicosatrienoic acids that induce arteriole dilation, and 20-HETE that induces arteriole constriction. In addition to actions on the vasculature, the release of chemical transmitters from astrocytes regulates neuronal function. Astrocyte-derived glutamate, which preferentially acts on extrasynaptic receptors, can promote neuronal synchrony, enhance neuronal excitability, and modulate synaptic transmission. Astrocyte-derived d-serine, by acting on the glycine-binding site of the N-methyl-d-aspartate receptor, can modulate synaptic plasticity. Astrocyte-derived ATP, which is hydrolyzed to adenosine in the extracellular space, has inhibitory actions and mediates synaptic cross-talk underlying heterosynaptic depression. Now that we appreciate this range of actions of astrocytic signaling, some of the immediate challenges are to determine how the astrocyte regulates neuronal integration and how both excitatory (glutamate) and inhibitory signals (adenosine) provided by the same glial cell act in concert to regulate neuronal function.
从结构角度来看，中枢神经系统中占主导地位的神经胶质细胞——星形胶质细胞，其位置使其能够调节突触传递和神经血管耦合：一个星形胶质细胞的突起与数以万计的突触相接触，而同一个细胞的其他突起则在毛细血管和小动脉上形成终足。目前，将Ca2+信号的亚细胞成像应用于星形胶质细胞，为支持这一结构概念提供了功能数据。星形胶质细胞表达多种神经递质的受体，其激活会导致细胞内Ca2+振荡。这些振荡会诱导花生四烯酸的积累以及化学递质谷氨酸、D-丝氨酸和ATP的释放。星形胶质细胞终足中的Ca2+振荡可通过花生四烯酸代谢产物前列腺素E2和环氧二十碳三烯酸（它们可诱导小动脉扩张）以及20-羟基二十碳四烯酸（它可诱导小动脉收缩）来控制脑微循环。除了对血管系统的作用外，星形胶质细胞释放的化学递质还能调节神经元功能。星形胶质细胞衍生的谷氨酸优先作用于突触外受体，可促进神经元同步性、增强神经元兴奋性并调节突触传递。星形胶质细胞衍生的D-丝氨酸通过作用于N-甲基-D-天冬氨酸受体的甘氨酸结合位点，可调节突触可塑性。星形胶质细胞衍生的ATP在细胞外空间水解为腺苷，具有抑制作用，并介导异突触抑制背后的突触间相互作用。既然我们已经了解了星形胶质细胞信号传导的这一系列作用，那么一些紧迫的挑战就是确定星形胶质细胞如何调节神经元整合，以及同一个神经胶质细胞提供的兴奋性（谷氨酸）和抑制性信号（腺苷）如何协同作用来调节神经元功能。
