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GABA mediates presynaptic inhibition at glycinergic synapses in a rat auditory brainstem nucleus

Lim, Rebecca; Alvarez, Francisco; Walmsley, Bruce

Description

1. Many inhibitory nerve terminals in the mammalian anteroventral cochlear nucleus (AVCN) contain both glycine and GABA, but the reason for the co-localization of these two inhibitory neurotransmitters in the AVCN is unknown. We have investigated the roles of glycine and GABA at synapses on bushy cells in the rat AVCN, using receptor immunohistochemistry and electrophysiology. 2. Our immunohistochemical results show prominent punctate labelling of postsynaptic clusters of glycine receptors and...[Show more]

dc.contributor.authorLim, Rebecca
dc.contributor.authorAlvarez, Francisco
dc.contributor.authorWalmsley, Bruce
dc.date.accessioned2015-12-13T23:16:13Z
dc.identifier.issn0022-3751
dc.identifier.urihttp://hdl.handle.net/1885/89291
dc.description.abstract1. Many inhibitory nerve terminals in the mammalian anteroventral cochlear nucleus (AVCN) contain both glycine and GABA, but the reason for the co-localization of these two inhibitory neurotransmitters in the AVCN is unknown. We have investigated the roles of glycine and GABA at synapses on bushy cells in the rat AVCN, using receptor immunohistochemistry and electrophysiology. 2. Our immunohistochemical results show prominent punctate labelling of postsynaptic clusters of glycine receptors and of the receptor clustering protein gephyrin over the surface of bushy cells. In contrast, weak diffuse membrane immunolabelling of GABA(A) receptors was observed. 3. Whole-cell recordings from bushy cells in AVCN slices demonstrated that evoked inhibitory postsynaptic currents (IPSCs) were predominantly (81%) glycinergic, based on the decrease in amplitude of the IPSCs in bicuculline (10 μM). This observation was supported by the effect of strychnine (1 μM), which was to decrease the evoked IPSC (to 10% of control IPSC amplitude) and to produce a greater than 90% block of spontaneous miniature IPSCs. 4. These results suggest a minor role for postsynaptic GABA(A) receptors in bushy cells, despite a high proportion of GABA-containing terminals on these cells. Therefore, a role for metabotropic GABA(B) receptors was investigated. Activation of GABA(B) receptors with baclofen revealed a significant attenuation of evoked glycinergic IPSCs. The effect of baclofen was presynaptic, as indicated by a lack of change in the mean amplitude of spontaneous IPSCs. 5. Significantly, the decrease in the amplitude of evoked glycinergic IPSCs observed following repetitive nerve stimulation was reduced in the presence of the GABA(B) antagonist, CGP 35348. This indicates that synaptically released GABA can activate presynaptic GABA(B) receptors to reduce transmitter release at glycinergic synapses. Our results suggest specific pre- versus postsynaptic physiological roles for GABA and glycine in the AVCN.
dc.publisherCambridge University Press
dc.sourceJournal of Physiology
dc.subjectKeywords: 3 aminopropyl(diethoxymethyl)phosphinic acid; 4 aminobutyric acid; 4 aminobutyric acid A receptor; 4 aminobutyric acid B receptor; baclofen; gephyrin; glycine; glycine receptor; neurotransmitter; strychnine; animal tissue; article; brain stem; cochlear nu
dc.titleGABA mediates presynaptic inhibition at glycinergic synapses in a rat auditory brainstem nucleus
dc.typeJournal article
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.citationvolume525
dc.date.issued2000
local.identifier.absfor060105 - Cell Neurochemistry
local.identifier.ariespublicationMigratedxPub19261
local.type.statusPublished Version
local.contributor.affiliationLim, Rebecca, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationAlvarez, Francisco, Wright State University
local.contributor.affiliationWalmsley, Bruce, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.startpage447
local.bibliographicCitation.lastpage459
dc.date.updated2015-12-12T08:47:08Z
local.identifier.scopusID2-s2.0-0034212866
CollectionsANU Research Publications

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