Astrocytes exhibit diverse Ca²⁺ changes at subcellular domains during brain aging

Astrocytic Ca²⁺ transients are essential for astrocyte integration into neural circuits. These Ca²⁺ transients are primarily sequestered in subcellular domains, including primary branches, branchlets and leaflets, and endfeet. In previous studies, it suggests that aging causes functional defects in astrocytes. Until now, it was unclear whether and how aging affects astrocytic Ca²⁺ transients at subcellular domains. In this study, we combined a genetically encoded Ca²⁺ sensor (GCaMP6f) and in vivo two-photon Ca²⁺ imaging to determine changes in Ca²⁺ transients within astrocytic subcellular domains during brain aging. We showed that aging increased Ca²⁺ transients in astrocytic primary branches, higher-order branchlets, and terminal leaflets. However, Ca²⁺ transients decreased within astrocytic endfeet during brain aging, which could be caused by the decreased expressions of Aquaporin-4 (AQP4). In addition, aging-induced changes of Ca²⁺ transient types were heterogeneous within astrocytic subcellular domains. These results demonstrate that the astrocytic Ca²⁺ transients within subcellular domains are affected by aging differently. This finding contributes to a better understanding of the physiological role of astrocytes in aging-induced neural circuit degeneration.