PKMzeta maintains memories by regulating GluR2-dependent AMPA receptor trafficking.
The maintenance of long-term memory in hippocampus, neocortex and amygdala requires the persistent action of the atypical protein kinase C isoform, protein kinase Mzeta (PKMzeta). We found that inactivating PKMzeta in the amygdala impaired fear memory in rats and that the extent of the impairment was positively correlated with a decrease in postsynaptic GluR2. Blocking the GluR2-dependent removal of postsynaptic AMPA receptors abolished the behavioral impairment caused by PKMzeta inhibition and the associated decrease in postsynaptic GluR2 expression, which correlated with performance. Similarly, blocking this pathway for removal of GluR2-containing receptors from postsynaptic sites in amygdala slices prevented the reversal of long-term potentiation caused by inactivating PKMzeta. Similar behavioral results were obtained in the hippocampus for unreinforced recognition memory of object location. Together, these findings indicate that PKMzeta maintains long-term memory by regulating the trafficking of GluR2-containing AMPA receptors, the postsynaptic expression of which directly predicts memory retention.
Migues
Paola Virginia
PV
Department of Psychology, McGill University, Montreal, Quebec, Canada. virginia.migues@mcgill.ca
Hardt
Oliver
O
Wu
Dong Chuan
DC
Gamache
Karine
K
Sacktor
Todd Charlton
TC
Wang
Yu Tian
YT
Nader
Karim
K
D000704:Analysis of Variance; D000818:Animals; D001360:Avidin / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D019921:Biotinylation / Q000379:methods; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004597:Electroshock / Q000009:adverse effects; D005239:Fear / Q000187:drug effects; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D006624:Hippocampus / Q000502:physiology / Q000648:ultrastructure; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010455:Peptides / Q000494:pharmacology; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D018709:Statistics, Nonparametric; D013347:Subcellular Fractions / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D010455:Peptides; D018091:Receptors, AMPA; C093483:neutravidin; D001360:Avidin; D011493:Protein Kinase C; C504730:protein kinase M zeta, rat; C104722:glutamate receptor ionotropic, AMPA 2
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