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mGluR control of interneuron output regulates feedforward tonic GABAA inhibition in the visual thalamus

Errington, Adam Clarke, Di Giovanni, Giuseppe, Crunelli, Vincenzo and Cope, David William 2011. mGluR control of interneuron output regulates feedforward tonic GABAA inhibition in the visual thalamus. Journal of Neuroscience 31 (23) , pp. 8669-8680. 10.1523/JNEUROSCI.0317-11.2011

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Abstract

Metabotropic glutamate receptors (mGluRs) play a crucial role in regulation of phasic inhibition within the visual thalamus. Here we demonstrate that mGluR-dependent modulation of interneuron GABA release results in dynamic changes in extrasynaptic GABAA receptor (eGABAAR)-dependent tonic inhibition in thalamocortical (TC) neurons of the rat dorsal lateral geniculate nucleus (dLGN). Application of the group I selective mGluR agonist dihydroxyphenylglycine produces a concentration-dependent enhancement of both IPSC frequency and tonic GABAA current (IGABAtonic) that is due to activation of both mGluR1a and mGluR5 subtypes. In contrast, group II/III mGluR activation decreases both IPSC frequency and IGABAtonic amplitude. Using knock-out mice, we show that the mGluR-dependent modulation of IGABAtonic is dependent upon expression of δ-subunit containing eGABAARs. Furthermore, unlike the dLGN, no mGluR-dependent modulation of IGABAtonic is present in TC neurons of the somatosensory ventrobasal thalamus, which lacks GABAergic interneurons. In the dLGN, enhancement of IPSC frequency and IGABAtonic by group I mGluRs is not action potential dependent, being insensitive to TTX, but is abolished by the L-type Ca2+ channel blocker nimodipine. These results indicate selective mGluR-dependent modulation of dendrodendritic GABA release from F2-type terminals on interneuron dendrites and demonstrate for the first time the presence of eGABAARs on TC neuron dendritic elements that participate in “triadic” circuitry within the dLGN. These findings present a plausible novel mechanism for visual contrast gain at the thalamic level and shed new light upon the potential role of glial ensheathment of synaptic triads within the dLGN.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Neuroscience and Mental Health Research Institute (NMHRI)
Medicine
Subjects: Q Science > Q Science (General)
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Additional Information: Pdf uploaded in accordance with publisher's policy at http://www.jneurosci.org/site/misc/ifa_policies.xhtml#copyright (accessed 26/02/2014).
Publisher: Society for Neuroscience
ISSN: 0270-6474
Date of First Compliant Deposit: 30 March 2016
Last Modified: 05 Apr 2018 09:43
URI: http://orca-mwe.cf.ac.uk/id/eprint/24323

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