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Pre- and Postsynaptic Activation of GABA-B Receptors Modulates Principal Cell Excitation in the Piriform Cortex

Gerrard, Leah; Tantirigama, Malinda; Bekkers, John

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The piriform cortex (PC), like other cortical regions, normally operates in a state of dynamic equilibrium between excitation and inhibition. Here we examined the roles played by pre- and postsynaptic GABAB receptors in maintaining this equilibrium in the PC. Using whole-cell recordings in brain slices from the anterior PC of mice, we found that synaptic activation of postsynaptic GABAB receptors hyperpolarized the two major classes of layer 2 principal neurons and reduced the intrinsic...[Show more]

dc.contributor.authorGerrard, Leah
dc.contributor.authorTantirigama, Malinda
dc.contributor.authorBekkers, John
dc.date.accessioned2021-03-15T23:59:55Z
dc.date.available2021-03-15T23:59:55Z
dc.identifier.citationGerrard LB, Tantirigama MLS and Bekkers JM (2018) Pre- and Postsynaptic Activation of GABAB Receptors Modulates Principal Cell Excitation in the Piriform Cortex. Front. Cell. Neurosci. 12:28. doi: 10.3389/fncel.2018.00028
dc.identifier.issn1662-5102
dc.identifier.urihttp://hdl.handle.net/1885/227192
dc.description.abstractThe piriform cortex (PC), like other cortical regions, normally operates in a state of dynamic equilibrium between excitation and inhibition. Here we examined the roles played by pre- and postsynaptic GABAB receptors in maintaining this equilibrium in the PC. Using whole-cell recordings in brain slices from the anterior PC of mice, we found that synaptic activation of postsynaptic GABAB receptors hyperpolarized the two major classes of layer 2 principal neurons and reduced the intrinsic electrical excitability of these neurons. Presynaptic GABAB receptors are expressed on the terminals of associational (intracortical) glutamatergic axons in the PC. Heterosynaptic activation of these receptors reduced excitatory associational inputs onto principal cells. Presynaptic GABAB receptors are also expressed on the axons of GABAergic interneurons in the PC, and blockade of these autoreceptors enhanced inhibitory inputs onto principal cells. Hence, presynaptic GABAB autoreceptors produce disinhibition of principal cells. To study the functional consequences of GABAB activation in vivo, we used 2-photon calcium imaging to simultaneously monitor the activity of ~200 layer 2 neurons. Superfusion of the GABAB agonist baclofen reduced spontaneous random firing but also promoted synchronous epileptiform activity. These findings suggest that, while GABAB activation can dampen excitability by engaging pre- and postsynaptic GABAB heteroreceptors on glutamatergic neurons, it can also promote excitability by disinhibiting principal cells by activating presynaptic GABAB autoreceptors on interneurons. Thus, depending on the dynamic balance of hetero- and autoinhibition, GABAB receptors can function as variable modulators of circuit excitability in the PC.
dc.description.sponsorshipThis work was supported by the National Health and Medical Research Council of Australia (Project Grants 1050832 and 1128320 to JMB), by recurrent funding from the John Curtin School of Medical Research (JCSMR) to JMB, and by a JCSMR Honours scholarship to LBG.
dc.format.mimetypeapplication/pdf
dc.language.isoen_AU
dc.publisherFrontiers Research Foundation
dc.rights© 2018 Gerrard, Tantirigama and Bekkers
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceFrontiers in Cellular Neuroscience
dc.subject2-photon
dc.subjectepilepsy
dc.subjectGABAB
dc.subjectmodulation
dc.subjectpiriform cortex
dc.titlePre- and Postsynaptic Activation of GABA-B Receptors Modulates Principal Cell Excitation in the Piriform Cortex
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume12
dcterms.dateAccepted2018-01-18
dc.date.issued2018-02-05
local.identifier.absfor110906 - Sensory Systems
local.identifier.ariespublicationu6414078xPUB1
local.publisher.urlhttps://www.frontiersin.org/
local.type.statusPublished Version
local.contributor.affiliationGerrard, Leah, College of Health and Medicine, ANU
local.contributor.affiliationTantirigama, Malinda, College of Health and Medicine, ANU
local.contributor.affiliationBekkers, John, College of Health and Medicine, ANU
dc.relationhttp://purl.org/au-research/grants/nhmrc/1050832
dc.relationhttp://purl.org/au-research/grants/nhmrc/1128320
local.bibliographicCitation.issue28
local.bibliographicCitation.startpage1
local.bibliographicCitation.lastpage11
local.identifier.doi10.3389/fncel.2018.00028
dc.date.updated2020-11-23T11:51:30Z
local.identifier.scopusID2-s2.0-85043524312
dcterms.accessRightsOpen Access
dc.provenanceThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.rights.licenseCreative Commons Attribution License (CC BY)
CollectionsANU Research Publications

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