Ca2+ signaling in astrocytes from Ip3r2−/− mice in brain slices and during startle responses in vivo

• Published in: Nature neuroscience Vol. 18; no. 5; pp. 708 - 717
• Main Authors: Srinivasan, Rahul, Huang, Ben S, Venugopal, Sharmila, Johnston, April D, Chai, Hua, Zeng, Hongkui, Golshani, Peyman, Khakh, Baljit S
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 20-04-2015; Nature Publishing Group
• Subjects: 14; 14/35; 14/63; 14/69; 38; 631/378/2596/1308; 631/378/340; 96; 96/109; 96/63; Animal Genetics and Genomics; Automation; Behavioral Sciences; Biological Techniques; Biomedicine; Medicine; Microscopy; Neurobiology; Neurosciences; Physiology; Quantum dots; Software; Los Angeles California; United States > US; California
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn.4001

In this manuscript, the authors use state-of-the-art imaging methods to report the discovery of novel forms of astrocyte calcium signaling in wild-type mice and in mutant mice previously thought to lack astrocyte calcium dynamics. The findings have important implications for experimental and theoretical studies of astrocyte functions in neural circuits.
Intracellular Ca
2+
signaling is considered to be important for multiple astrocyte functions in neural circuits. However, mice devoid of inositol triphosphate type 2 receptors (IP3R2) reportedly lack all astrocyte Ca
2+
signaling, but display no neuronal or neurovascular deficits, implying that astrocyte Ca
2+
fluctuations are not involved in these functions. An assumption has been that the loss of somatic Ca
2+
fluctuations also reflects a similar loss in astrocyte processes. We tested this assumption and found diverse types of Ca
2+
fluctuations in astrocytes, with most occurring in processes rather than in somata. These fluctuations were preserved in
Ip3r2
−/−
(also known as
Itpr2
−/−
) mice in brain slices and
in vivo
, occurred in end feet, and were increased by G protein–coupled receptor activation and by startle-induced neuromodulatory responses. Our data reveal previously unknown Ca
2+
fluctuations in astrocytes and highlight limitations of studies that used
Ip3r2
−/−
mice to evaluate astrocyte contributions to neural circuit function and mouse behavior.