Astrocytic PAR1 and mGluR2/3 control synaptic glutamate time course at hippocampal CA1 synapses

• Published in: Glia Vol. 72; no. 9; pp. 1707 - 1724
• Main Authors: Roh, Woo Suk, Yoo, Jae Hong, Dravid, Shashank M., Mannaioni, Guido, Krizman, Elizabeth N., Wahl, Philip, Robinson, Michael B., Traynelis, Stephen F., Lee, C. Justin, Han, Kyung‐Seok
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.09.2024; Wiley Subscription Services, Inc
• Subjects: astrocyte; Astrocytes; electrophysiology; G protein-coupled receptors; glutamate; Glutamic acid receptors (metabotropic); Glutamic acid transporter; Hippocampus; mGluR2/3; PAR1; Receptors; Regulatory mechanisms (biology); Synapses; Synaptic cleft; Synaptic transmission; Synaptogenesis; mGluR2/3; electrophysiology; PAR1; astrocyte; glutamate
• ISSN: 0894-1491; 1098-1136; 1098-1136
• DOI: 10.1002/glia.24579

Astrocytes play an essential role in regulating synaptic transmission. This study describes a novel form of modulation of excitatory synaptic transmission in the mouse hippocampus by astrocytic G‐protein‐coupled receptors (GPCRs). We have previously described astrocytic glutamate release via protease‐activated receptor‐1 (PAR1) activation, although the regulatory mechanisms for this are complex. Through electrophysiological analysis and modeling, we discovered that PAR1 activation consistently increases the concentration and duration of glutamate in the synaptic cleft. This effect was not due to changes in the presynaptic glutamate release or alteration in glutamate transporter expression. However, blocking group II metabotropic glutamate receptors (mGluR2/3) abolished PAR1‐mediated regulation of synaptic glutamate concentration, suggesting a role for this GPCR in mediating the effects of PAR1 activation on glutamate release. Furthermore, activation of mGluR2/3 causes glutamate release through the TREK‐1 channel in hippocampal astrocytes. These data show that astrocytic GPCRs engage in a novel regulatory mechanism to shape the time course of synaptically‐released glutamate in excitatory synapses of the hippocampus. Main Points Astrocytic PAR1 activation increases synaptic glutamate in the mouse hippocampus. Astrocytic mGluR2/3 is responsible for PAR1‐mediated synaptic glutamate increases.