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After naturalistic odor preference training, Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) was rapidly phosphorylated in the olfactory bulb, specifically in the odor encoding regions of the glomerular layer and external plexiform layer. Intrabulbar CaMKII antagonist experiments revealed that CaMKII supports short- and long-term preference memory formation. With bulbar PKA activation as the unconditioned stimulus odor preferences could be induced despite CaMKII blockade, but now odor specificity was lost, with odor preference generalizing to an untrained odor. Odor-specific learning was associated with increased membrane-associated AMPA receptors, while nonspecific odor preference was not. Thus CaMKII activation provides a tag to confer stimulus specificity as well as supporting natural odor preference learning.

CaMKII mediates stimulus specificity in early odor preference learning in rats