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dc.contributor.authorZeredo, Jorge Len
dc.contributor.authorQuah, Shaunen
dc.contributor.authorWallis, Chloe Uen
dc.contributor.authorAlexander, Laithen
dc.contributor.authorCockcroft, Gemmaen
dc.contributor.authorSantangelo, Andrea Marianaen
dc.contributor.authorXia, Jingen
dc.contributor.authorShiba, Yoshiroen
dc.contributor.authorDalley, Jeffreyen
dc.contributor.authorCardinal, Rudolfen
dc.contributor.authorRoberts, Angelaen
dc.contributor.authorClarke, Hannahen
dc.date.accessioned2019-01-30T00:30:37Z
dc.date.available2019-01-30T00:30:37Z
dc.date.issued2019-04en
dc.identifier.issn0270-6474
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/288499
dc.description.abstractHigh-trait anxiety is a risk factor for the development of affective disorders and has been associated with decreased cardiovascular and behavioral responsivity to acute stressors in humans that may increase the risk of developing cardiovascular disease. Although human neuroimaging studies of high-trait anxiety reveals dysregulation in primate cingulate areas 25 and 32 and the anterior hippocampus (aHipp), and rodent studies reveal the importance of aHipp glutamatergic hypofunction, the causal involvement of aHipp glutamate and its interaction with these areas in the primate brain is unknown. Accordingly, we correlated marmoset trait anxiety scores to their post-mortem aHipp glutamate levels, and showed that low glutamate in the right aHipp is associated with high trait anxiety in marmosets. Moreover, pharmacologically increasing aHipp glutamate reduced anxiety levels in high anxious marmosets in two uncertainty based tests of anxiety – exposure to a human intruder with uncertain intent, and unpredictable loud noise. In the human intruder test, increasing aHipp glutamate decreased anxiety by increasing approach to the intruder. In the unpredictable threat test, animals showed blunted behavioral and cardiovascular responsivity after control infusions, which was normalized by increasing aHipp glutamate. However, this aHipp-mediated anxiolytic effect was blocked by simultaneous pharmacological inactivation of area 25, but not 32 ‒ areas which when inactivated independently reduced, and had no effect on anxiety, respectively. These findings provide causal evidence in male and female primates that aHipp glutamatergic hypofunction, and its regulation by area 25, contributes to the behavioral and cardiovascular symptoms of endogenous high-trait anxiety.
dc.description.sponsorshipCNPq (Brazil), Malaysian Public Service Department
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherSociety for Neuroscience
dc.subjectHippocampusen
dc.subjectAnimalsen
dc.subjectCallithrixen
dc.subjectPhosphinic Acidsen
dc.subjectBenzylaminesen
dc.subjectXanthenesen
dc.subjectAmino Acidsen
dc.subjectGlutamic Aciden
dc.subjectExcitatory Amino Acid Antagonistsen
dc.subjectBehavior, Animalen
dc.subjectAnxietyen
dc.subjectHeart Rateen
dc.subjectFemaleen
dc.subjectMaleen
dc.subjectGABA-A Receptor Antagonistsen
dc.titleGlutamate Within the Marmoset Anterior Hippocampus Interacts with Area 25 to Regulate the Behavioral and Cardiovascular Correlates of High-Trait Anxiety.en
dc.typeArticle
prism.endingPage3107
prism.issueIdentifier16en
prism.publicationDate2019en
prism.publicationNameThe Journal of neuroscience : the official journal of the Society for Neuroscienceen
prism.startingPage3094
prism.volume39en
dc.identifier.doi10.17863/CAM.35786
dcterms.dateAccepted2018-12-14en
rioxxterms.versionofrecord10.1523/jneurosci.2451-18.2018en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-04en
dc.contributor.orcidZeredo, Jorge L [0000-0003-0338-5850]
dc.contributor.orcidQuah, Shaun Kit Lung [0000-0002-8857-1320]
dc.contributor.orcidWallis, Chloe U [0000-0002-6770-8324]
dc.contributor.orcidAlexander, Laith [0000-0003-1297-6548]
dc.contributor.orcidSantangelo, Andrea Mariana [0000-0001-7727-2651]
dc.contributor.orcidDalley, Jeffrey [0000-0002-2282-3660]
dc.contributor.orcidCardinal, Rudolf [0000-0002-8751-5167]
dc.contributor.orcidRoberts, Angela [0000-0003-2873-157X]
dc.contributor.orcidClarke, Hannah [0000-0002-1289-8917]
dc.identifier.eissn1529-2401
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (G1100307)
pubs.funder-project-idMedical Research Council (MR/M023990/1)
pubs.funder-project-idMRC (G1000183)
pubs.funder-project-idMEDICAL RESEARCH COUNCIL (G0001354)
cam.orpheus.successThu Jan 30 12:52:28 GMT 2020 - Embargo updated*
cam.orpheus.counter1*
rioxxterms.freetoread.startdate2019-10-30


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