| Annotated protein: | Metabotropic glutamate receptor 2 (mGluR2). Gene symbol: GRM2. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q14BI2 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ GRM2 |
| Ontology domain: | Biological Process |
| SynGO term: | presynaptic modulation of chemical synaptic transmission (GO:0099171) |
| Synapse type(s): | thalamus, glutamatergic |
| Annotated paper: | Joffe ME, et al. "mGlu(2) and mGlu(3) Negative Allosteric Modulators Divergently Enhance Thalamocortical Transmission and Exert Rapid Antidepressant-like Effects" Neuron. 2020 Jan 8;105(1):46-59.e3 PMID:31735403 |
| Figure(s): | Figs 2, 3(D-E), 4 |
| Annotation description: | "Pharmacological inhibition of mGlu2 increases glutamate release probability promoting thalamocortical transmission" In the experiments shown in this paper, cfos-EGFP or C57BL/6J mice are injected with a control/vehicle solution (eg. DMSO) or Negative Allosteric Modulators (NAMs) solutions for mGlu2 (VU6001966) and for mGlu3 (VU0650786, this protein will be not described in this annotation). After, slices from these mice are prepared to carry out electrophysiological recordings. In Fig.2, cFos-GFP-positive cells (which were activated by inhibiting mGlu2 with NAM) present a higher hyperpolarization sag, amplitude and frequency of AMPA-receptor-mediated spontaneous excitatory postsynaptic currents (sEPSCs) after mGlu2 NAM administration with respect to control condition. In Figs.3D-E, we observe again a notable increase of sEPSC amplitude and frequency after mGlu2 NAM administration (in slices from not cfos-EGFP mice this time), suggesting that inhibition of this receptor can stimulate glutamate transmission into the prefrontal cortex (PFC). In Fig.4, we can see how NAMs administration affects the axis Mediodorsal nucleus of the thalamus-Prefrontal cortex (MDT-PFC) in terms of glutamate transmission and it is studied in slices from mice where it is possible to visualize the optogenetic protein ChR2 (virally expressed previously). An increase of optically-induced EPSC and a decrease of paired-pulse ratio (PPR) is observed after mGlu2 NAM administration, findings that supporting an increase in presynaptic glutamate release probability when mGlu2 is inhibited. Notes: In Fig.1, a significant increase of cFos-positive cells is observed after mGlu2 NAM administration, indicating that inhibition of this receptor promotes the activation of the prefrontal cortex. In this case, the technique used is immunohistochemistry, not electrophysiology. In Fig.5, following with the study of the MDT-PFC axis at thalamocortical synapses, it is shown that mGlu2 NAM partially reduces postsynaptic long-term depression (LTD) in the PFC. |
| Evidence tracking, Biological System: | Intact tissue |
| Evidence tracking, Protein Targeting: | Antagonist / agonist |
| Evidence tracking, Experiment Assay: | Confocal Whole-cell patch clamp Optical physiology |
| Annotator(s): | Carlos Pascual-Caro (ORCID:0000-0002-2345-393X) Anjali Amrapali Vishwanath (ORCID:0000-0002-9888-0928) Jaime de Juan-Sanz (ORCID:0000-0002-1212-5623) |
| Lab: | ICM - Brain and Spine Institute, Hpital Piti Salptrire, 47 Boulevard de l'Hpital, 75013 Paris, France |
| Additional literature: | In this paper, it is observed how agonists for group II mGluRs (this group includes mGlu2/3 receptors) provoke a notable depression of excitatory transmission due mainly to inhibition of glutamate release from glutamatergic terminals innervating pyramidal cells. @ PMID:30670948 |
| SynGO annotation ID: | 4014 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |