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 m ale, during a critical period after mating. Failure to form this memor y results in the male being treated as strange, and hence, his pheromo nes block pregnancy. Previous studies have shown that formation of thi s memory is dependent on synaptic mechanisms in the accessory olfactor y bulb. A number of studies have pointed to calmodulin as a critical m ediator of synaptic plasticity. In this study we have examined the eff ects of local infusions of drugs which block calmodulin-regulated proc esses, into the accessory olfactory bulb on the formation of this memo ry. Infusions of the calmodulin antagonist calmidazolium during the cr itical period prevented memory formation. However, the specific inhibi tor of calcium/calmodulin-dependent protein kinase II, KN-62, or the s elective inhibitor of calcium/calmodulin-dependent protein phosphatase 2B (calcineurin), FK506, was without effect on memory formation at an y of the doses used. Instead of preventing memory formation, FK506 per mitted the formation of a non-selective memory to strange male pheromo nes in the presence of mating, although FK506 alone could not induce a memory without the occurrence of mating. These results suggest that c almodulin in the accessory olfactory bulb is important in the formatio n of the olfactory memory to male pheromones. However, memory formatio n may be independent of calmodulin-kinase II. Calcineurin may play a r ole in processes antagonizing memory formation.