Photochemically Initiated Intracellular Astrocytic Calcium Waves in Living Mice Using Two-Photon Uncaging of IP3

摘要

We have developed a caged IP3 analogue for two-photon photolysis in living animals. This probe is a cell permeable version and was coloaded with a fluorescent Ca²⁺ dye into astrocytes in layer 1 of the somatosensory cortex of anesthetized mice. Two-photon irradiation of single cells at 720 nm produced rapid and robust increases in intracellular Ca²⁺ concentrations monitored using two-photon microscopy at 950 nm. The photoevoked intracellular Ca²⁺ waves were similar in magnitude to intrinsic signals in wild type mice. These waves did not propagate to other cells beyond the targeted astrocyte. In contrast, we observed intercellular astrocytic Ca²⁺ waves in two mouse models of familial Alzheimer’s disease. These data suggest that Alzheimer’s might perturb gliotransmission but not IP3 signaling per se in mouse models of the disease.