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Papers of the Week

Papers: 19 Mar 2022 - 25 Mar 2022

Animal Studies, Pharmacology/Drug Development

2022 Apr 04

J Exp Med



Editor's Pick

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


Danjo Y, Shigetomi E, Hirayama YJ, Kobayashi K, Ishikawa T, Fukazawa Y, Shibata K, Takanashi K, Parajuli B, Shinozaki Y, Kim S K, Nabekura J, Koizumi S
J Exp Med. 2022 Apr 04; 219(4).
PMID: 35319723.


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.