Synaptic Inhibition in the Accessory Olfactory Bulb Regulates Pheromone Location Learning and Memory

Pheromone signaling is pivotal in driving the social and reproductive behaviors of rodents. Learning and memorizing the pheromone locations involve olfactory subsystems. To study the neural basis of this behavior, we trained female heterozygous knockouts of GluA2 (AMPAR subunit) and NR1 (NMDAR subunit), targeting GAD65 interneuron population, in a pheromone location learning assay. We observed impaired memory of pheromone locations on early and late recall periods, pointing towards the possible role of ionotropic glutamate receptors (iGluRs) and thereby the synaptic inhibition in pheromone location learning. Correlated changes were observed in the expression levels of activity-regulated cytoskeletal (Arc) protein, which is critical for memory consolidation, in the associated brain areas. Further, to probe the involvement of the main and accessory olfactory bulbs (MOB and AOB) in pheromone location learning, we knocked out GluA2 and NR1 from MOB and/or AOB neuronal circuits by stereotaxic injection of Cre-dependent AAV5 viral particles. Perturbing the inhibitory circuits of MOB and AOB or AOB-alone resulted in pheromone location memory deficits. These results confirm the role of iGluRs and the synaptic inhibition exerted by the interneuron network of AOB in regulating learning and memory of pheromone locations.