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

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http://hdl.handle.net/10138/312937

Lähdeviite

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

Julkaisun nimi: Kainate receptor auxiliary subunit NETO2 is required for normal fear expression and extinction
Tekijä: Mennesson, Marie; Rydgren, Emilie; Lipina, Tatiana; Sokolowska, Ewa; Kulesskaya, Natalia; Morello, Francesca; Ivakine, Evgueni; Voikar, Vootele; Risbrough, Victoria; Partanen, Juha; Hovatta, Iiris
Tekijän organisaatio: Biosciences
Molecular and Integrative Biosciences Research Programme
Department of Psychology and Logopedics
Neuroscience Center
Developmental neurogenetics
University Management
Iiris Hovatta / Principal Investigator
Genetics
Mind and Matter
Päiväys: 2019-10
Kieli: eng
Sivumäärä: 12
Kuuluu julkaisusarjaan: Neuropsychopharmacology
ISSN: 0893-133X
DOI-tunniste: https://doi.org/10.1038/s41386-019-0344-5
URI: http://hdl.handle.net/10138/312937
Tiivistelmä: 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.
Avainsanat: AMYGDALA
HIPPOCAMPUS
NEURONS
LOCALIZATION
ASSOCIATION
INVOLVEMENT
DISORDER
RELEASE
MEMORY
3112 Neurosciences
515 Psychology
Vertaisarvioitu: Kyllä
Pääsyrajoitteet: openAccess
Rinnakkaistallennettu versio: acceptedVersion


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