Transient astrocytic mGluR5 expression drives synaptic plasticity and subsequent chronic pain in mice

J Exp Med. 2022 Apr 4;219(4):e20210989. doi: 10.1084/jem.20210989. Epub 2022 Mar 23.


Activation of astrocytes has a profound effect on brain plasticity and is critical for the pathophysiology of several neurological disorders including neuropathic pain. Here, we show that metabotropic glutamate receptor 5 (mGluR5), which reemerges in astrocytes in a restricted time frame, is essential for these functions. Although mGluR5 is absent in healthy adult astrocytes, it transiently reemerges in astrocytes of the somatosensory cortex (S1). During a limited spatiotemporal time frame, astrocytic mGluR5 drives Ca2+ signals; upregulates multiple synaptogenic molecules such as Thrombospondin-1, Glypican-4, and Hevin; causes excess excitatory synaptogenesis; and produces persistent alteration of S1 neuronal activity, leading to mechanical allodynia. All of these events were abolished by the astrocyte-specific deletion of mGluR5. Astrocytes dynamically control synaptic plasticity by turning on and off a single molecule, mGluR5, which defines subsequent persistent brain functions, especially under pathological conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes* / metabolism
  • Chronic Pain* / pathology
  • Mice
  • Neuronal Plasticity
  • Neurons / metabolism
  • Receptor, Metabotropic Glutamate 5 / metabolism


  • Grm5 protein, mouse
  • Receptor, Metabotropic Glutamate 5