Learning-Induced Metaplasticity? Associative Training for Early Odor Preference Learning Down-Regulates Synapse-Specific NMDA Receptors via mGluR and Calcineurin Activation.
Rat pups readily form a 24-h associative odor preference after a single trial of odor paired with intermittent stroking. Recent evidence shows that this training trial, which normally increases AMPA receptor responses in the anterior piriform cortex both 3 and 24 h following training, induces a down-regulation of NMDA receptors 3 h later followed by NMDA receptor up-regulation at 24 h. When retrained with the same odor at 3 h, rat pups unlearn the original odor preference. Unlearning can be prevented by blocking NMDA receptors during retraining. Here, the mechanisms that initiate NMDA receptor down-regulation are assessed. Blocking mGluR receptors or calcineurin during training prevents down-regulation of NMDA receptors 3 h following training. Blocking NMDA receptors during training does not affect NMDA receptor down-regulation. Thus, down-regulation can be engaged separately from associative learning. When unlearning occurs, AMPA and NMDA receptor levels at 24 h are reset to control levels. Calcineurin blockade during retraining prevents unlearning consistent with the role of NMDA receptor down-regulation. The relationship of these events to the metaplasticity and plasticity mechanisms of long-term depression and depotentiation is discussed. We suggest a possible functional role of NMDA receptor down-regulation in offline stabilization of learned odor representations.
Division of Biomedical Sciences, Faculty of Medicine.
Bandhan
B
Mukherjee
Department of Psychology, Faculty of Science, Memorial University of Newfoundland, St. John's, NL, Canada.
Carolyn W
CW
Harley
Division of Biomedical Sciences, Faculty of Medicine.
Qi
Q
Yuan
D000818:Animals; D000831:Animals, Newborn; D001245:Association Learning / Q000187:drug effects / Q000502:physiology*; D019703:Calcineurin / Q000378:metabolism*; D005786:Gene Expression Regulation; D008568:Memory / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D055696:Olfactory Perception / Q000187:drug effects / Q000502:physiology*; D066195:Piriform Cortex / Q000187:drug effects / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D019703:Calcineurin
NMDA receptor; metaplasticity; olfactory learning; piriform cortex; plasticity