Astrocytic mGluR5 Regulation of Synaptic Transmission is Activity-Dependent in Adult Rats

Data accumulated over the last two decades have demonstrated that astrocytes play key roles in the regulation of synaptic transmission and plasticity. This is due, among other mechanisms, to their capability to detect and regulate synaptic transmission by expressing receptors and releasing gliotransmitters, respectively. Importantly, in juvenile rats, astrocytes are able to detect glutamate release at the level of individual synapses through mGluR5 and consequently up-regulate excitatory synaptic transmission efficacy through the release of purines. Whether this upregulation is still present in the adult brain is an open question. Using immunohistochemistry and RNAscope on fixed tissue, as well as electrophysiological recordings on acute hippocampal brain slices of adult male rats, we demonstrated that this regulatory pathway also prevails in adult rats. Most surprisingly, such facilitation of glutamate release that is readily observed when a small number of synapses are activated was completely abolished under conditions where a large number of inputs were stimulated. These findings thus suggest that astrocytes integrate the incoming afferent information and adapt their responses depending on the network activity.