PT  - JOURNAL ARTICLE
AU  - Bandhan Mukherjee
AU  - Gillian L. Morrison
AU  - Christine J. Fontaine
AU  - Qinlong Hou
AU  - Carolyn W. Harley
AU  - Qi Yuan
TI  - Unlearning: NMDA Receptor-Mediated Metaplasticity in the Anterior Piriform Cortex Following Early Odor Preference Training in Rats
AID  - 10.1523/JNEUROSCI.0128-14.2014
DP  - 2014 Apr 09
TA  - The Journal of Neuroscience
PG  - 5143--5151
VI  - 34
IP  - 15
4099  - http://www.jneurosci.org/content/34/15/5143.short
4100  - http://www.jneurosci.org/content/34/15/5143.full
SO  - J. Neurosci.2014 Apr 09; 34
AB  - 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.