title: Profound desensitization by ambient GABA limits activation of δ-containing GABAA receptors during spillover.
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 δ 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" δ 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.
authors.affiliation: Biophysics Section, Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: Damian P
authors.initials: DP
authors.lastname: Bright
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Renzi
authors.forename: Julian
authors.initials: J
authors.lastname: Bartram
authors.forename: Thomas P
authors.initials: TP
authors.lastname: McGee
authors.forename: Georgina
authors.initials: G
authors.lastname: MacKenzie
authors.forename: Alastair M
authors.initials: AM
authors.lastname: Hosie
authors.forename: Mark
authors.initials: M
authors.lastname: Farrant
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Brickley
mesh_terms: D000818:Animals; D002460:Cell Line; D002531:Cerebellum / Q000166:cytology / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000502:physiology; D051381:Rats; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D013788:Thalamus / Q000166:cytology / Q000502:physiology; D014162:Transfection; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D021122:Protein Subunits; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid