title: Acquisition of conditioned fear is followed by region-specific changes in RNA editing of glutamate receptors.
abstract: Adenosine (A) to inosine (I) RNA editing is a post-transcriptional modification process that can affect synaptic function. Transcripts encoding the kainate GRIK1 and AMPA GluA2 glutamate receptor subunits undergo editing that leads to a glycine/arginine (Q/R) exchange and reduced Ca(2+) permeability. We hypothesized that editing at these sites could be experience-dependent, temporally dynamic and region-specific. We trained C57/Bl6 mice in trace and contextual fear conditioning protocols, and examined editing levels at GRIK1 and GluA2 Q/R sites in the amygdala (CeA) and hippocampus (CA1 and CA3), at two time points after training. We also examined experience-dependent changes in the expression of RNA editing enzymes and editing targets. Animals trained in the trace fear conditioning protocol exhibited a transient increase in unedited GRIK1 RNA in the amygdala, and their learning efficiency correlated with unedited RNA levels in CA1. In line with previous reports, GluA2 RNA editing levels were nearly 100%. Additionally, we observed experience-dependent changes in mRNA expression of the RNA editing enzymes ADAR2 and ADAR1 in amygdala and hippocampus, and a learning-dependent increase in the alternatively spliced inactive form of ADAR2 in the amygdala. Since unedited transcripts code for Ca(2+)-permeable receptor subunits, these findings suggest that RNA editing at Q/R sites of glutamate receptors plays an important role in experience-dependent synaptic modification processes.
authors.affiliation: a Psychology Department , University of Haifa , Haifa , Israel and.
authors.forename: Noa
authors.initials: N
authors.lastname: Brande-Eilat
authors.affiliation: a Psychology Department , University of Haifa , Haifa , Israel and.
authors.forename: Yaela N
authors.initials: YN
authors.lastname: Golumbic
authors.affiliation: a Psychology Department , University of Haifa , Haifa , Israel and.
authors.forename: Hiba
authors.initials: H
authors.lastname: Zaidan
authors.affiliation: a Psychology Department , University of Haifa , Haifa , Israel and.|b Department of Psychiatry , Columbia University , New York , NY , USA.
authors.forename: Inna
authors.initials: I
authors.lastname: Gaisler-Salomon
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics*; D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003213:Conditioning, Psychological; D004644:Emotions; D005239:Fear; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017393:RNA Editing; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics*; D018091:Receptors, AMPA / Q000235:genetics*; D018092:Kainic Acid Receptors / Q000235:genetics*
chemical_list: D000243:Adenosine Deaminase; D002118:Calcium; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; C000599465:ADAR1 protein, mouse; C000595151:ADAR2 protein, mouse; C104722:glutamate receptor ionotropic, AMPA 2
keywords: ADAR; AMPA; Glutamate; RNA editing; calcium; fear conditioning; kainate; mouse