Format

Send to

Choose Destination
J Physiol. 2012 Feb 15;590(4):937-51. doi: 10.1113/jphysiol.2011.218065. Epub 2011 Dec 23.

Positive allosteric modulation reveals a specific role for mGlu2 receptors in sensory processing in the thalamus.

Author information

1
Department of Visual Neuroscience, UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK. c.copeland@ucl.ac.uk

Abstract

Group II metabotropic glutamate receptor (mGlu) modulation of sensory processing in the rat ventrobasal thalamic nucleus (VB) has been extensively studied in vivo. However, it is not yet known what the relative contributions are of the Group II mGlu receptor subtypes (mGlu2 and mGlu3) to this modulation, nor to what extent these receptors may be activated under physiological conditions during this process. Using single-neurone recording in the rat VB in vivo with local application of the selective Group II agonist LY354740 and the subtype selective mGlu2 positive allosteric modulator (PAM) LY487379, our findings were twofold. Firstly, we found that there is an mGlu2 component to the effects of LY354740 on sensory responses in the VB. Secondly, we have demonstrated that application of the PAM alone can modulate sensory responses of single neurones in vivo. This indicates that mGlu2 receptors can be activated by endogenous agonist following physiological sensory stimulation. We speculate that the mGlu2 subtype could be activated under physiological stimulus-evoked conditions by 'glutamate spillover' from synapses between excitatory sensory afferents and VB neurones that can lead to a reduction in sensory-evoked inhibition arising from the thalamic reticular nucleus (TRN). We propose that this potential mGlu2 receptor modulation of inhibition could play an important role in discerning relevant information from background activity upon physiological sensory stimulation. Furthermore, this could be a site of action for mGlu2 PAMs to modulate cognitive processes.

PMID:
22199165
PMCID:
PMC3381320
DOI:
10.1113/jphysiol.2011.218065
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center