| First Author | Copeland CS | Year | 2022 |
| Journal | Br J Pharmacol | Volume | 179 |
| Issue | 8 | Pages | 1607-1619 |
| PubMed ID | 34355803 | Mgi Jnum | J:331633 |
| Mgi Id | MGI:7386954 | Doi | 10.1111/bph.15640 |
| Citation | Copeland CS, et al. (2022) Group II metabotropic glutamate receptor (mGlu(2) and mGlu(3) ) roles in thalamic processing. Br J Pharmacol 179(8):1607-1619 |
| abstractText | BACKGROUND AND PURPOSE: As the thalamus underpins almost all aspects of behaviour, it is important to understand how the thalamus operates. Group II metabotropic glutamate (mGlu(2) /mGlu(3) ) receptor activation reduces inhibition in thalamic nuclei originating from the surrounding thalamic reticular nucleus (TRN). Whilst an mGlu(2) component to this effect has been reported, in this study, we demonstrate that it is likely, largely mediated via mGlu(3) . EXPERIMENTAL APPROACH: The somatosensory ventrobasal thalamus (VB) is an established model for probing fundamental principles of thalamic function. In vitro slices conserving VB-TRN circuitry from wild-type and mGlu(3) knockout mouse brains were used to record IPSPs and mIPSCs. In vivo extracellular recordings were made from VB neurons in anaesthetised rats. A range of selective pharmacological agents were used to probe Group II mGlu receptor function (agonist, LY354740; antagonist, LY341495; mGlu(2) positive allosteric modulator, LY487379 and mixed mGlu(2) agonist/mGlu(3) antagonist LY395756). KEY RESULTS: The in vitro and in vivo data are complementary and suggest that mGlu(3) receptor activation is largely responsible for potentiating responses to somatosensory stimulation by reducing inhibition from the TRN. CONCLUSIONS AND IMPLICATIONS: mGlu(3) receptor activation in the VB likely enables important somatosensory information to be discerned from background activity. These mGlu(3) receptors are likely to be endogenously activated via 'glutamate spillover'. In cognitive thalamic nuclei, this mechanism may be of importance in governing attentional processes. Positive allosteric modulation of endogenous mGlu(3) receptor activation may therefore enhance cognitive function in pathophysiological disease states, such as schizophrenia, thus representing a highly specific therapeutic target. LINKED ARTICLES: This article is part of a themed issue on Building Bridges in Neuropharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.8/issuetoc. |
