Revisiting metaplasticity: The roles of calcineurin and histone deacetylation in unlearning odor preference memory in rat pups.

Previous work has shown that 24 h duration odor preference learning, induced by one-trial training, generates a down-regulation of the GluN1 receptor in anterior piriform cortex at 3 h, and results in metaplastic unlearning if a second training trial is given at 3 h. The GluN1 receptor upregulates at 24 h so 24 h spaced training is highly effective in extending memory duration. The present study replicates the piriform cortex unlearning result in the olfactory bulb circuit and further studies the relationship between the initial training strength and its associated metaplastic effect. Intrabulbar infusions that block calcineurin or inhibit histone deacetylation normally produce extended days-long memory. If given during training, they are not associated with GluN1 downregulation at 3 h and do not recruit an unlearning process at that time. The two memory strengthening protocols do not appear to interact, but are also not synergistic. These outcomes argue that it is critical to understand the metaplastic effects of training in order to optimize training protocols in the service of either memory strengthening or of memory weakening.