CNRS UMR 8118, Brain Physiology Laboratory, F-75006 Paris, France; Fédération de Recherche en Neurosciences FR3636, Faculté de Sciences Fondamentales et Biomédicales, Université Paris Descartes, PRES Université Sorbonne Paris Cité (USPC), F-75006 Paris, France.
CNRS UMR 8118, Brain Physiology Laboratory, F-75006 Paris, France; Fédération de Recherche en Neurosciences FR3636, Faculté de Sciences Fondamentales et Biomédicales, Université Paris Descartes, PRES Université Sorbonne Paris Cité (USPC), F-75006 Paris, France.
Brain Res Bull. 2018 Jan;136:54-64. doi: 10.1016/j.brainresbull.2017.04.011. Epub 2017 Apr 24.
Astrocytes are a neural cell type critically involved in maintaining brain energy homeostasis as well as signaling. Like neurons, astrocytes are a heterogeneous cell population. Cortical astrocytes show a complex morphology with a highly branched aborization and numerous fine processes ensheathing the synapses of neighboring neurons, and typically extend one process connecting to blood vessels. Recent studies employing genetically encoded fluorescent calcium (Ca) indicators have described 'spontaneous' localized Ca-transients in the astrocyte periphery that occur asynchronously, independently of signals in other parts of the cells, and that do not involve somatic Ca transients; however, neither it is known whether these Ca-microdomains occur at or near neuronal synapses nor have their molecular basis nor downstream effector(s) been identified. In addition to Ca microdomains, sodium (Na) transients occur in astrocyte subdomains, too, most likely as a consequence of Na co-transport with the neurotransmitter glutamate, which also regulates mitochondrial movements locally - as do cytoplasmic Ca levels. In this review, we cover various aspects of these local signaling events and discuss how structural and biophysical properties of astrocytes might foster such compartmentation. Astrocytes metabolically interact with neurons by providing energy substrates to active neurons. As a single astrocyte branch covers hundreds to thousands of synapses, it is tempting to speculate that these metabolic interactions could occur localized to specific subdomains of astrocytes, perhaps even at the level of small groups of synapses. We discuss how astrocytic metabolism might be regulated at this scale and which signals might contribute to its regulation. We speculate that the astrocytic structures that light up transiently as Ca-microdomains might be the functional units of astrocytes linking signaling and metabolic processes to adapt astrocytic function to local energy demands. The understanding of these local regulatory and metabolic interactions will be fundamental to fully appreciate the complexity of brain energy homeostasis as well as its failure in disease and may shed new light on the controversy about neuron-glia bi-directional signaling at the tripartite synapse.
星形胶质细胞是一种神经细胞类型，在维持脑能量平衡以及信号传递方面起着至关重要的作用。与神经元一样，星形胶质细胞是一种异质细胞群体。大脑皮层星形胶质细胞具有复杂的形态，其分支高度分支，并有许多细小的突起包裹着邻近神经元的突触，通常会延伸出一个与血管相连的突起。最近的研究利用遗传编码的荧光钙（Ca）指示剂描述了星形胶质细胞外周的“自发性”局部 Ca 瞬变，这些瞬变是异步发生的，与细胞其他部位的信号无关，也不涉及体细胞 Ca 瞬变；然而，目前尚不清楚这些 Ca 微区是否发生在神经元突触附近，也不清楚其分子基础或下游效应物（s）是什么。除了 Ca 微区外，钠（Na）瞬变也会发生在星形胶质细胞亚区，这很可能是由于 Na 与神经递质谷氨酸共转运的结果，谷氨酸也会局部调节线粒体的运动 - 就像细胞质 Ca 水平一样。在这篇综述中，我们涵盖了这些局部信号事件的各个方面，并讨论了星形胶质细胞的结构和生物物理特性如何促进这种分隔。星形胶质细胞通过向活跃的神经元提供能量底物来与神经元进行代谢相互作用。由于单个星形胶质细胞分支覆盖数百到数千个突触，因此人们不禁推测，这些代谢相互作用可能发生在星形胶质细胞的特定亚区，甚至可能发生在一小群突触上。我们讨论了如何在这种规模上调节星形胶质细胞的代谢，以及哪些信号可能有助于其调节。我们推测，Ca 微区中短暂点亮的星形胶质细胞结构可能是将信号和代谢过程联系起来以适应星形胶质细胞功能以满足局部能量需求的功能性单位。理解这些局部调节和代谢相互作用对于充分理解脑能量平衡的复杂性及其在疾病中的失败至关重要，并可能为三突触神经元-胶质双向信号传递的争议提供新的线索。
