Downregulation of kainate receptors regulating GABAergic transmission in amygdala after early life stress is associated with anxiety-like behavior in rodents

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Englund , J , Haikonen , J , Shteinikov , V , Amarilla , S P , Atanasova , T , Shintyapina , A , Ryazantseva , M , Partanen , J , Voikar , V & Lauri , S E 2021 , ' Downregulation of kainate receptors regulating GABAergic transmission in amygdala after early life stress is associated with anxiety-like behavior in rodents ' , Translational Psychiatry , vol. 11 , no. 1 , 538 . https://doi.org/10.1038/s41398-021-01654-7

Title: Downregulation of kainate receptors regulating GABAergic transmission in amygdala after early life stress is associated with anxiety-like behavior in rodents
Author: Englund, Jonas; Haikonen, Joni; Shteinikov, Vasilii; Amarilla, Shyrley Paola; Atanasova, Tsvetomira; Shintyapina, Alexandra; Ryazantseva, Maria; Partanen, Juha; Voikar, Vootele; Lauri, Sari E.
Contributor: University of Helsinki, Syn­aptic Plas­ti­city and De­vel­op­ment
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, Neuroscience Center
University of Helsinki, Veterinary Biosciences
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
Date: 2021-10-18
Language: eng
Number of pages: 15
Belongs to series: Translational Psychiatry
ISSN: 2158-3188
URI: http://hdl.handle.net/10138/335772
Abstract: Early life stress (ELS) is a well-characterized risk factor for mood and anxiety disorders. GABAergic microcircuits in the amygdala are critically implicated in anxiety; however, whether their function is altered after ELS is not known. Here we identify a novel mechanism by which kainate receptors (KARs) modulate feedforward inhibition in the lateral amygdala (LA) and show that this mechanism is downregulated after ELS induced by maternal separation (MS). Specifically, we show that in control rats but not after MS, endogenous activity of GluK1 subunit containing KARs disinhibit LA principal neurons during activation of cortical afferents. GluK1 antagonism attenuated excitability of parvalbumin (PV)-expressing interneurons, resulting in loss of PV-dependent inhibitory control and an increase in firing of somatostatin-expressing interneurons. Inactivation of Grik1 expression locally in the adult amygdala reduced ongoing GABAergic transmission and was sufficient to produce a mild anxiety-like behavioral phenotype. Interestingly, MS and GluK1-dependent phenotypes showed similar gender specificity, being detectable in male but not female rodents. Our data identify a novel KAR-dependent mechanism for cell-type and projection-specific functional modulation of the LA GABAergic microcircuit and suggest that the loss of GluK1 KAR function contributes to anxiogenesis after ELS.
Subject: BASOLATERAL AMYGDALA
SYNAPTIC-TRANSMISSION
GENE-EXPRESSION
SEX-DIFFERENCES
GABA RELEASE
INTERNEURONS
ADULT
FEAR
ACTIVATION
ALTERS
3112 Neurosciences
3124 Neurology and psychiatry
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