Unlearning: NMDA receptor-mediated metaplasticity in the anterior piriform cortex following early odor preference training in rats.
Here we demonstrate metaplastic effect of a change in NMDA receptor (NMDAR) number in the anterior piriform cortex (aPC) in rat induced by a 10 min pairing of peppermint odor + stroking, which significantly modifies later learning and memory. Using isolated synaptoneurosomes, we found NR1 receptor downregulation 3 h after training and upregulation at 24 h. Consistent with the NR1 pattern, the NMDAR-mediated EPSP was smaller at 3 h and larger at 24 h. Subunit composition was unchanged. Whereas LTP was reduced at both times by training, LTD was facilitated only at 3 h. Behaviorally, pups, given a pairing of peppermint + stroking 3 h after an initial peppermint + stroking training, lost the normally acquired peppermint preference 24 h later. To probe the pathway specificity of this unlearning effect, pups were trained first with peppermint and then, at 3 h, given a second training with peppermint or vanillin. Pups given peppermint training at both times lost the learned peppermint preference. Pups given vanillin retraining at 3 h had normal peppermint preference. Downregulating NR1 with siRNA prevented odor preference learning. Finally, the NMDAR antagonist MK-801 blocked the LTD facilitation seen 3 h after training, and giving MK-801 before the second peppermint training trial eliminated the loss of peppermint odor preference. A training-associated reduction in NMDARs facilitates LTD 3 h later; training at the time of LTD facilitation reverses an LTP-dependent odor preference. Experience-dependent, pathway-specific metaplastic effects in a cortical structure have broad implications for the optimal spacing of learning experiences.
Division of Biomedical Sciences, Faculty of Medicine and Department of Psychology, Faculty of Science, Memorial University of Newfoundland, St. John's, Newfoundland A1B 3V6, Canada, and Neuroscience Program, Victoria University, Victoria, British Columbia V8P 5C2, Canada.
Bandhan
B
Mukherjee
Gillian L
GL
Morrison
Christine J
CJ
Fontaine
Qinlong
Q
Hou
Carolyn W
CW
Harley
Qi
Q
Yuan
D000818:Animals; D003214:Conditioning, Classical; D004192:Discrimination, Psychological; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D007858:Learning; D017774:Long-Term Potentiation; D008297:Male; D009833:Olfactory Pathways / Q000378:metabolism / Q000502:physiology*; D055696:Olfactory Perception; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate
LTD; LTP; NMDAR; olfactory learning; piriform cortex; rat