Acquisition of conditioned fear is followed by region-specific changes in RNA editing of glutamate receptors

Noa Brande-Eilat, Yaela N. Golumbic, Hiba Zaidan, Inna Gaisler-Salomon

Research output: Contribution to journalArticlepeer-review

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 Ca2+ 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 Ca2+-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.

Original languageEnglish
Pages (from-to)309-318
Number of pages10
JournalStress
Volume18
Issue number3
DOIs
StatePublished - 4 May 2015

Bibliographical note

Publisher Copyright:
© 2015 Taylor and Francis.

Keywords

  • ADAR
  • AMPA
  • Glutamate
  • RNA editing
  • calcium
  • fear conditioning
  • kainate
  • mouse

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Neuropsychology and Physiological Psychology
  • Psychiatry and Mental health
  • Physiology
  • Behavioral Neuroscience

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