Neuro-Electronics Research Flanders (NERF), Kapeldreef 75, 3001 Leuven, Belgium; VIB Center for Brain and Disease Research, Herestraat 49-Box 602, 3000 Leuven, Belgium.
Neuro-Electronics Research Flanders (NERF), Kapeldreef 75, 3001 Leuven, Belgium; IMEC, Kapeldreef 75, 3001 Leuven, Belgium.
Curr Biol. 2019 Sep 23;29(18):3120-3127.e5. doi: 10.1016/j.cub.2019.07.078. Epub 2019 Sep 5.
Astrocytes are a major cell type in the mammalian nervous system, are in close proximity to neurons, and show rich Ca activity thought to mediate cellular outputs. Astrocytes show activity linked to sensory [1, 2] and motor [3, 4] events, reflecting local neural activity and brain-wide neuromodulatory inputs. Sensory responses are highly variable [5-10], which may reflect interactions between distinct input types [6, 7, 9]. However, the diversity of inputs generating astrocyte activity, particularly during sensory stimulation and behavior, is not fully understood [11, 12]. Using a combination of Ca imaging, a treadmill assay, and visual stimulation, we examined the properties of astrocyte activity in mouse visual cortex associated with motor or sensory events. Consistent with previous work, motor activity activated astrocytes across the cortex with little specificity, reflecting a diffuse neuromodulatory mechanism. In contrast, moving visual stimuli generated specific activity patterns that reflected the stimulus' trajectory within the visual field, precisely as one would predict if astrocytes reported local neural activity. Visual responses depended strongly on behavioral state, with astrocytes showing high amplitude Ca transients during locomotion and little activity during stillness. Furthermore, the amplitudes of visual responses were highly correlated with pupil size, suggesting a role of arousal. Interestingly, while depletion of cortical noradrenaline abolished locomotor responses, visual responses were only reduced in amplitude and their spatiotemporal organization remained intact, suggesting two distinct types of inputs underlie visual responses. We conclude that cortical astrocytes integrate local sensory information and behavioral state, suggesting a role in information processing.
星形胶质细胞是哺乳动物神经系统中的主要细胞类型，与神经元紧密相邻，并表现出丰富的 Ca 活动，被认为介导细胞输出。星形胶质细胞表现出与感觉[1,2]和运动[3,4]事件相关的活动，反映了局部神经活动和全脑神经调制输入。感觉反应高度可变[5-10]，这可能反映了不同输入类型之间的相互作用[6,7,9]。然而，产生星形胶质细胞活动的输入多样性，特别是在感觉刺激和行为期间，还不完全清楚[11,12]。我们使用 Ca 成像、跑步机测定和视觉刺激的组合，研究了与运动或感觉事件相关的小鼠视觉皮层中星形胶质细胞活动的特性。与先前的工作一致，运动活动以一种非特异性的方式激活了整个皮层的星形胶质细胞，反映了一种弥漫的神经调制机制。相比之下，移动视觉刺激产生了特定的活动模式，反映了刺激在视野内的轨迹，这与如果星形胶质细胞报告局部神经活动，人们会预测到的情况完全一致。视觉反应强烈依赖于行为状态，在运动时星形胶质细胞表现出高振幅的 Ca 瞬变，而在静止时几乎没有活动。此外，视觉反应的振幅与瞳孔大小高度相关，这表明唤醒作用。有趣的是，虽然皮层去甲肾上腺素耗竭消除了运动反应，但视觉反应仅在幅度上减小，其时空组织仍然完整，这表明视觉反应的基础是两种不同类型的输入。我们得出结论，皮层星形胶质细胞整合局部感觉信息和行为状态，这表明它们在信息处理中发挥作用。
