The role of RNA editing of kainate receptors in synaptic plasticity and seizures.
The ionotropic glutamate receptor subunit GluR6 undergoes developmentally and regionally regulated Q/R site RNA editing that reduces the calcium permeability of GluR6-containing kainate receptors. To investigate the functional significance of this editing in vivo, we engineered mice deficient in GluR6 Q/R site editing. In these mutant mice but not in wild types, NMDA receptor-independent long-term potentiation (LTP) could be induced at the medial perforant path-dentate gyrus synapse. This indicates that kainate receptors with unedited GluR6 subunits can mediate LTP. Behavioral analyses revealed no differences from wild types, but mutant mice were more vulnerable to kainate-induced seizures. Together, these results suggest that GluR6 Q/R site RNA editing may modulate synaptic plasticity and seizure vulnerability.
Vissel
B
B
Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, CA 92037, USA. vissel@salk.edu
Royle
G A
GA
Christie
B R
BR
Schiffer
H H
HH
Ghetti
A
A
Tritto
T
T
Perez-Otano
I
I
Radcliffe
R A
RA
Seamans
J
J
Sejnowski
T
T
Wehner
J M
JM
Collins
A C
AC
O'Gorman
S
S
Heinemann
S F
SF
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007608:Kainic Acid; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D019580:Perforant Pathway / Q000166:cytology / Q000378:metabolism; D017393:RNA Editing / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000235:genetics / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D000097806:GluK2 Kainate Receptor
D002118:Calcium; D007608:Kainic Acid; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor