Ca(2+) signaling in astrocytes from Ip3r2(-/-) mice in brain slices and during startle responses in vivo

Nat Neurosci. 2015 May;18(5):708-17. doi: 10.1038/nn.4001. Epub 2015 Apr 20.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Animals
  • Astrocytes / physiology*
  • Astrocytes / ultrastructure
  • Calcium Signaling / physiology*
  • Crosses, Genetic
  • Female
  • Fluorescent Dyes
  • Hippocampus / cytology
  • Hippocampus / physiology
  • Inositol 1,4,5-Trisphosphate Receptors / deficiency*
  • Inositol 1,4,5-Trisphosphate Receptors / genetics
  • Male
  • Mice
  • Mice, Transgenic
  • Prazosin / pharmacology
  • Reflex, Startle / drug effects
  • Reflex, Startle / physiology*
  • Software


  • Fluorescent Dyes
  • Inositol 1,4,5-Trisphosphate Receptors
  • Ip3r2 protein, mouse
  • Prazosin