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 olfactory bulb, whose synaptic activities are modified by pheromonal inputs 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 specific pheromonal memory without mating by acting in synergy with bulbar neurotransmitter(s) to enhance long-lasting increase in gain of the mitral-granule cell dendrodendritic synapse. Two infusions of sodium nitroprusside (5 nmol; 0.5 microliters) into the accessory olfactory bulb activated recognition without mating. A single infusion produced no recognition. This memory is specific to the pheromones to which the females were exposed during sodium nitroprusside infusions because strange male pheromones evoked a significant pregnancy failure rate. Furthermore, the memory formation is dependent on coincident activation by pheromonal inputs and sodium nitroprusside infusions, since drug infusions in the absence of male pheromones permitted a significant pregnancy block on test exposure. The alpha-adrenergic antagonist phentolamine prevented a sodium nitroprusside-mediated memory formation. In females with depleted bulbar noradrenergic innervation by specific neurotoxin (6-hydroxydopamine) injection into the medial olfactory striae or the accessory olfactory bulb, sodium nitroprusside infusions failed to induce memory 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 olfactory memory without mating, and that this memory is mediated, at least in part, by noradrenaline.