Abstract
Q/R editing of kainate receptor (KAR) subunit GluK2 pre-mRNA replaces a genetically encoded glutamine to an arginine residue in the channel pore to alter the biophysical and trafficking properties of assembled KARs in recombinant systems. However, the consequences of GluK2 Q/R editing in vivo remain largely unexplored. Here we investigated differences between GluK2-editing deficient mice, that express ∼95% unedited GluK2(Q) compared to wild-type counterparts that express ∼85% edited GluK2(R). At hippocampal mossy fibre-CA3 (MF-CA3) synapses the editing-deficient (GluK2(Q)) mice displayed enhanced postsynaptic KAR function and increased KAR-mediated presynaptic facilitation, demonstrating heightened ionotropic function. Conversely, KAR-mediated metabotropic function, measured by regulation of afterhyperpolarization currents, was reduced in GluK2(Q) mice. Moreover, GluK2(Q) mice had fewer GluA1-containing synaptic AMPA receptors (AMPARs) and reduced postsynaptic AMPAR currents at MF-CA3 synapses. Using patterns of stimulation that replicate physiological activity, we show that GluK2(Q) mice have reduced long-term potentiation of AMPAR-mediated transmission at Schaffer collateral synapses. These findings indicate that GluK2 Q/R editing influences the balance of ionotropic versus metabotropic KAR signalling and regulates synaptic AMPAR expression and plasticity.
Competing Interest Statement
The authors have declared no competing interest.
