Astrocytes, the predominant type of glial cells, are attracting considerable attention as a potential target of drug discovery and therapeutics for neurodegenerative diseases. Astrocytic Ca2+ signals are enhanced by neuronal hyperactivities and/or bioactive substances released from injured brain cells, which can trigger astrocytic Ca2+-dependent processes including various gene expression and secretion of neuro-protective/toxic molecules. Thus, monitoring and analysis of astrocytic Ca2+ signals may provide clues to the regulation of neurodegenerative diseases. However, it remains elusive how the pathological conditions affect astrocytic Ca2+ activities. To address this issue, we are trying to establish a method to analyze in vivo astrocytic Ca2+ activities in neurodegenerative diseases. We generated a drug-induced neurodegenerative disease model using a transgenic mouse line expressing genetically encoded Ca2+ indicator, YC-Nano50, in astrocytes. Performing brain surface Ca2+ imaging in these mice, we found disorder-related changes in astrocytic Ca2+ activities. Thus, this method may contribute to the development of therapeutic strategies for neurodegenerative diseases.