In Vivo Visualization of Subtle, Transient, and Local Activity of Astrocytes Using an Ultrasensitive Ca2+ Indicator

• Developing a transgenic mouse line expressing an ultrasensitive Ca2+ indicator
• Ca2+ signals in the fine processes of astrocytes can be clearly visualized in vivo
• We visualize fine process-delimited spontaneous Ca2+ signals, termed Ca2+ twinkle
• The fine processes of astrocytes act as high-sensitivity detectors of neuron activity

SummaryAstrocytes generate local calcium (Ca2+) signals that are thought to regulate their functions. Visualization of these signals in the intact brain requires an imaging method with high spatiotemporal resolution. Here, we describe such a method using transgenic mice expressing the ultrasensitive ratiometric Ca2+ indicator yellow Cameleon-Nano 50 (YC-Nano50) in astrocytes. In these mice, we detected a unique pattern of Ca2+ signals. These occur spontaneously, predominantly in astrocytic fine processes, but not the cell body. Upon sensory stimulation, astrocytes initially responded with Ca2+ signals at fine processes, which then propagated to the cell body. These observations suggest that astrocytic fine processes function as a high-sensitivity detector of neuronal activities. Thus, the method provides a useful tool for studying the activity of astrocytes in brain physiology and pathology.

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