The importance of calmodulin in the accessory olfactory bulb in the formation of an olfactory memory in mice.

Female mice form an olfactory memory to the pheromones of the mating male, during a critical period after mating. Failure to form this memory results in the male being treated as strange, and hence, his pheromones block pregnancy. Previous studies have shown that formation of this memory is dependent on synaptic mechanisms in the accessory olfactory bulb. A number of studies have pointed to calmodulin as a critical mediator of synaptic plasticity. In this study we have examined the effects of local infusions of drugs which block calmodulin-regulated processes, into the accessory olfactory bulb on the formation of this memory. Infusions of the calmodulin antagonist calmidazolium during the critical period prevented memory formation. However, the specific inhibitor of calcium/calmodulin-dependent protein kinase II, KN-62, or the selective inhibitor of calcium/calmodulin-dependent protein phosphatase 2B (calcineurin), FK506, was without effect on memory formation at any of the doses used. Instead of preventing memory formation, FK506 permitted the formation of a non-selective memory to strange male pheromones in the presence of mating, although FK506 alone could not induce a memory without the occurrence of mating. These results suggest that calmodulin in the accessory olfactory bulb is important in the formation of the olfactory memory to male pheromones. However, memory formation may be independent of calmodulin-kinase II. Calcineurin may play a role in processes antagonizing memory formation.