Electron Microscopy Core Facility, Max Planck Florida Institute for Neuroscience, Jupiter, Florida, USA.
Department of Physiology and Biophysics, University of Colorado Denver, Aurora, Colorado, USA.
Glia. 2024 Oct;72(10):1785-1800. doi: 10.1002/glia.24582. Epub 2024 Jun 10.
Most excitatory synapses in the mammalian brain are contacted or ensheathed by astrocyte processes, forming tripartite synapses. Astrocytes are thought to be critical regulators of the structural and functional dynamics of synapses. While the degree of synaptic coverage by astrocytes is known to vary across brain regions and animal species, the reason for and implications of this variability remains unknown. Further, how astrocyte coverage of synapses relates to in vivo functional properties of individual synapses has not been investigated. Here, we characterized astrocyte coverage of synapses of pyramidal neurons in the ferret visual cortex and, using correlative light and electron microscopy, examined their relationship to synaptic strength and sensory-evoked Ca activity. Nearly, all synapses were contacted by astrocytes, and most were contacted along the axon-spine interface. Structurally, we found that the degree of synaptic astrocyte coverage directly scaled with synapse size and postsynaptic density complexity. Functionally, we found that the amount of astrocyte coverage scaled with how selectively a synapse responds to a particular visual stimulus and, at least for the largest synapses, scaled with the reliability of visual stimuli to evoke postsynaptic Ca events. Our study shows astrocyte coverage is highly correlated with structural metrics of synaptic strength of excitatory synapses in the visual cortex and demonstrates a previously unknown relationship between astrocyte coverage and reliable sensory activation.
哺乳动物大脑中的大多数兴奋性突触都被星形胶质细胞的突起接触或包裹,形成三突触。星形胶质细胞被认为是突触结构和功能动态的关键调节者。虽然星形胶质细胞对突触的覆盖程度因脑区和动物物种而异,但这种变异性的原因和意义仍不清楚。此外,星形胶质细胞对突触的覆盖程度与单个突触的体内功能特性有何关系尚未得到研究。在这里,我们描述了雪貂视觉皮层锥体神经元突触的星形胶质细胞覆盖情况,并使用相关的光和电子显微镜检查了它们与突触强度和感觉诱发 Ca 活动的关系。几乎所有的突触都被星形胶质细胞接触,而且大多数突触都沿着轴突-棘突界面接触。在结构上,我们发现突触星形胶质细胞覆盖的程度直接与突触大小和突触后密度复杂性成正比。在功能上,我们发现星形胶质细胞的覆盖程度与突触对特定视觉刺激的选择性反应程度成正比,至少对于最大的突触,与视觉刺激诱发突触后 Ca 事件的可靠性成正比。我们的研究表明,星形胶质细胞的覆盖程度与视觉皮层兴奋性突触的结构强度指标高度相关,并证明了星形胶质细胞覆盖程度与可靠的感觉激活之间以前未知的关系。