Impairment of olfactory memory by local infusions of non-selective excitatory amino acid receptor antagonists into the accessory olfactory bulb

Abstract

Female mice form a long-term olfactory memory to the pheromones of the male that mates with them. This memory is dependent on neural mechanisms within the accessory olfactory bulb. In this study we show that localized infusions of the excitatory amino acid receptor blocker, gamma-D-glutamylglycine, into the accessory olfactory bulb prevents memory formation. This is in marked contrast to the effects of infusions of the specific N-methyl-D-aspartate receptor antagonists, D-2-amino-5-phosphonovaleric acid and MK 801, which are without effect on memory formation. Excitatory amino acid receptor blockade by localized infusion of these drugs into the accessory olfactory bulb induced seizures. This paradoxical effect could only be due to disinhibition of granule cell GABAergic inhibitory feedback to the mitral cell. This was confirmed by the pregnancy blocking effect of these drugs, an event which also occurs with bicuculline infusions into the accessory olfactory bulb. These findings strongly implicate excitatory amino acid receptors in memory formation to the pheromones of the mating male and localize the mechanism to the reciprocal dendro-dendritic synapse between mitral and granule cells.