FORMATION OF AN OLFACTORY RECOGNITION MEMORY IN MICE - REASSESSMENT OF THE ROLE OF NITRIC-OXIDE

The plexiform and granule cell layers of the female mouse accessory ol factory bulb, whose synaptic activities are modified by pheromonal inp uts after mating, contain one of the highest densities of nitric oxide synthase in the brain. We tested the hypothesis that exogenous nitric oxide administration can, in principle, permit the formation of a spe cific pheromonal memory without mating by acting in I synergy with bul bar neurotransmitter(s) to enhance long-lasting increase in gain of th e mitral-granule cell dendrodendritic synapse. Two infusions of sodium nitroprusside (5 nnol; 0.5 mu l) into the accessory olfactory bulb ac tivated recognition without mating. A single infusion produced no reco gnition. This memory is specific to the pheromones to which the female s were exposed during sodium nitroprusside infusions because strange m ale pheromones evoked a significant pregnancy failure rate. Furthermor e, the memory formation is dependent on coincident activation by phero monal inputs and sodium nitroprusside infusions, since drug infusions in the absence of male pheromones permitted a significant pregnancy bl ock on test exposure. The cc-adrenergic antagonist phentolamine preven ted sodium nitroprusside-mediated memory formation. Ih females with de pleted bulbar noradrenergic innervation by specific neurotoxin (6-hydr oxydopamine) injection into the medial olfactory striae or the accesso ry olfactory bulb, sodium nitroprusside infusions failed to induce mem ory formation. The procedure itself apparently did not interfere with the occurrence of pregnancy. These results demonstrate that exogenous administration of nitric oxide can induce a pheromone-specific olfacto ry memory without mating, and that this memory is mediated, at least i n part, by noradrenaline.