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Profound Desensitization by Ambient GABA Limits Activation of delta-Containing GABA(A) Receptors during Spillover

Bright, DP; Renzi, M; Bartram, J; McGee, TP; MacKenzie, G; Hosie, AM; Farrant, M; (2011) Profound Desensitization by Ambient GABA Limits Activation of delta-Containing GABA(A) Receptors during Spillover. J NEUROSCI , 31 (2) 753 - 763. 10.1523/JNEUROSCI.2996-10.2011.

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Abstract

High-affinity extrasynaptic GABA(A) receptors (GABA(A)Rs) are a prominent feature of cerebellar granule neurons and thalamic relay neurons. In both cell types, the presence of synaptic glomeruli would be expected to promote activation of these GABA(A)Rs, contributing to phasic spillover-mediated currents and tonic inhibition. However, the precise role of different receptor subtypes in these two phenomena is unclear. To address this question, we made recordings from neurons in acute brain slices from mice, and from tsA201 cells expressing recombinant GABA(A)Rs. We found that delta subunit-containing GABA(A)Rs of both cerebellar granule neurons and thalamic relay neurons of the lateral geniculate nucleus contributed to tonic conductance caused by ambient GABA but not to spillover-mediated currents. In the presence of a low "ambient" GABA concentration, recombinant "extrasynaptic" delta subunit-containing GABA(A)Rs exhibited profound desensitization, rendering them insensitive to brief synaptic-or spillover-like GABA transients. Together, our results demonstrate that phasic spillover and tonic inhibition reflect the activation of distinct receptor populations.

Type: Article
Title: Profound Desensitization by Ambient GABA Limits Activation of delta-Containing GABA(A) Receptors during Spillover
DOI: 10.1523/JNEUROSCI.2996-10.2011
Keywords: CEREBELLAR GRANULE CELLS, SUBUNIT-DEFICIENT MICE, THALAMIC RELAY NEURONS, TONIC INHIBITION, NEUROSTEROID MODULATION, NEUROACTIVE STEROIDS, ALTERED EXPRESSION, AMINO-ACIDS, RAT, RELEASE
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/705847
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