In Vivo visualization of subtle, transient, and local activity of astrocytes using an ultrasensitive Ca²⁺ indicator

Astrocytes 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) inastrocytes. 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.