Kainate Receptor Auxiliary Subunit NETO2-Related Cued Fear Conditioning Impairments Associate with Defects in Amygdala Development and Excitability

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Mennesson , M , Orav , E , Gigliotta , A , Kulesskaya , N , Saarnio , S , Kirjavainen , A , Kesaf , S , Winkel , F , Llach Pou , M , Umemori , J , Voikar , V , Risbrough , V , Partanen , J , Castrén , E , Lauri , S E & Hovatta , I 2020 , ' Kainate Receptor Auxiliary Subunit NETO2-Related Cued Fear Conditioning Impairments Associate with Defects in Amygdala Development and Excitability ' , eNeuro , vol. 7 , no. 4 . https://doi.org/10.1523/ENEURO.0541-19.2020

Title: Kainate Receptor Auxiliary Subunit NETO2-Related Cued Fear Conditioning Impairments Associate with Defects in Amygdala Development and Excitability
Author: Mennesson, Marie; Orav, Ester; Gigliotta, Adrien; Kulesskaya, Natalia; Saarnio, Suvi; Kirjavainen, Anna; Kesaf, Sebnem; Winkel, Frederike; Llach Pou, Maria; Umemori, Juzoh; Voikar, Vootele; Risbrough, Victoria; Partanen, Juha; Castrén, Eero; Lauri, Sari E.; Hovatta, Iiris
Contributor: University of Helsinki, Department of Psychology and Logopedics
University of Helsinki, Syn­aptic Plas­ti­city and De­vel­op­ment
University of Helsinki, SLEEPWELL Research Program
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, STEMM - Stem Cells and Metabolism Research Program
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, Syn­aptic Plas­ti­city and De­vel­op­ment
University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
University of Helsinki, Developmental neurogenetics
University of Helsinki, Neuroscience Center
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, Department of Psychology and Logopedics
Date: 2020-07-01
Language: eng
Belongs to series: eNeuro
ISSN: 2373-2822
URI: http://hdl.handle.net/10138/324672
Abstract: NETO2 is an auxiliary subunit for kainate-type glutamate receptors that mediate normal cued fear expression and extinction. Since the amygdala is critical for these functions, we asked whether Neto2−/− mice have compromised amygdala function. We measured the abundance of molecular markers of neuronal maturation and plasticity, parvalbumin-positive (PV+), perineuronal net-positive (PNN+), and double positive (PV+PNN+) cells in the Neto2−/− amygdala. We found that Neto2−/− adult, but not postnatal day (P)23, mice had 7.5% reduction in the fraction of PV+PNN+ cells within the total PNN+ population, and 23.1% reduction in PV staining intensity compared with Neto2+/+ mice, suggesting that PV interneurons in the adult Neto2−/− amygdala remain in an immature state. An immature PV inhibitory network would be predicted to lead to stronger amygdalar excitation. In the amygdala of adult Neto2−/− mice, we identified increased glutamatergic and reduced GABAergic transmission using whole-cell patch-clamp recordings. This was accompanied by increased spine density of thin dendrites in the basal amygdala (BA) compared with Neto2+/+ mice, indicating stronger glutamatergic synapses. Moreover, after fear acquisition Neto2−/− mice had a higher number of c-Fos-positive cells than Neto2+/+ mice in the lateral amygdala (LA), BA, and central amygdala (CE). Altogether, our findings indicate that Neto2 is involved in the maturation of the amygdala PV interneuron network. Our data suggest that this defect, together with other processes influencing amygdala principal neurons, contribute to increased amygdalar excitability, higher fear expression, and delayed extinction in cued fear conditioning, phenotypes that are common in fear-related disorders, including the posttraumatic stress disorder (PTSD).
Subject: 3112 Neurosciences
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