Kainate receptor auxiliary subunit NETO2 is required for normal fear expression and extinction

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dc.contributor.author Mennesson, Marie
dc.contributor.author Rydgren, Emilie
dc.contributor.author Lipina, Tatiana
dc.contributor.author Sokolowska, Ewa
dc.contributor.author Kulesskaya, Natalia
dc.contributor.author Morello, Francesca
dc.contributor.author Ivakine, Evgueni
dc.contributor.author Voikar, Vootele
dc.contributor.author Risbrough, Victoria
dc.contributor.author Partanen, Juha
dc.contributor.author Hovatta, Iiris
dc.date.accessioned 2020-03-05T03:34:38Z
dc.date.available 2021-12-18T03:45:55Z
dc.date.issued 2019-10
dc.identifier.citation Mennesson , M , Rydgren , E , Lipina , T , Sokolowska , E , Kulesskaya , N , Morello , F , Ivakine , E , Voikar , V , Risbrough , V , Partanen , J & Hovatta , I 2019 , ' Kainate receptor auxiliary subunit NETO2 is required for normal fear expression and extinction ' , Neuropsychopharmacology , vol. 44 , no. 11 , pp. 1855-1866 . https://doi.org/10.1038/s41386-019-0344-5
dc.identifier.other PURE: 127213112
dc.identifier.other PURE UUID: 31e216fe-9518-43e1-817d-aed8de7de578
dc.identifier.other WOS: 000485776700004
dc.identifier.other ORCID: /0000-0002-5990-7892/work/62631407
dc.identifier.other ORCID: /0000-0003-4201-8666/work/62632520
dc.identifier.other ORCID: /0000-0001-5517-8525/work/62632891
dc.identifier.other ORCID: /0000-0003-0889-4590/work/62633302
dc.identifier.uri http://hdl.handle.net/10138/312937
dc.description.abstract NETO1 and NETO2 are auxiliary subunits of kainate receptors (KARs). They interact with native KAR subunits to modulate multiple aspects of receptor function. Variation in KAR genes has been associated with psychiatric disorders in humans, and in mice, knockouts of the Grik1 gene have increased, while Grik2 and Grik4 knockouts have reduced anxiety-like behavior. To determine whether the NETO proteins regulate anxiety and fear through modulation of KARs, we undertook a comprehensive behavioral analysis of adult Neto1(-/-) and Neto2(-/-) mice. We observed no differences in anxiety-like behavior. However, in cued fear conditioning, Neto2(-/-), but not Neto1(-/-) mice, showed higher fear expression and delayed extinction compared to wild type mice. We established, by in situ hybridization, that Neto2 was expressed in both excitatory and inhibitory neurons throughout the fear circuit including the medial prefrontal cortex, amygdala, and hippocampus. Finally, we demonstrated that the relative amount of synaptosomal KAR GLUK2/3 subunit was 20.8% lower in the ventral hippocampus and 36.5% lower in the medial prefrontal cortex in Neto2(-/-) compared to the Neto2(+/+) mice. The GLUK5 subunit abundance was reduced 23.8% in the ventral hippocampus and 16.9% in the amygdala. We conclude that Neto2 regulates fear expression and extinction in mice, and that its absence increases conditionability, a phenotype related to post-traumatic stress disorder and propose that this phenotype is mediated by reduced KAR subunit abundance at synapses of fear-associated brain regions. en
dc.format.extent 12
dc.language.iso eng
dc.relation.ispartof Neuropsychopharmacology
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject AMYGDALA
dc.subject HIPPOCAMPUS
dc.subject NEURONS
dc.subject ASSOCIATION
dc.subject INVOLVEMENT
dc.subject DISORDER
dc.subject RELEASE
dc.subject MEMORY
dc.subject 3112 Neurosciences
dc.subject 515 Psychology
dc.title Kainate receptor auxiliary subunit NETO2 is required for normal fear expression and extinction en
dc.type Article
dc.contributor.organization Biosciences
dc.contributor.organization Molecular and Integrative Biosciences Research Programme
dc.contributor.organization Department of Psychology and Logopedics
dc.contributor.organization Neuroscience Center
dc.contributor.organization Developmental neurogenetics
dc.contributor.organization University Management
dc.contributor.organization Iiris Hovatta / Principal Investigator
dc.contributor.organization Genetics
dc.contributor.organization Mind and Matter
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1038/s41386-019-0344-5
dc.relation.issn 0893-133X
dc.rights.accesslevel openAccess
dc.type.version acceptedVersion

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