Synaptic inhibition in the accessory olfactory bulb regulates pheromone location learning and memory

Abstract

Pheromone signaling is pivotal in driving 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 place preference learning assay. We observed memory loss 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 main olfactory bulb (MOB) and accessory olfactory bulb (AOB) in pheromone location learning, we knocked out NR1 and GluA2 from MOB and/or AOB neuronal circuits by stereotaxic injection of Cre-dependent AAV5 viral particles. Perturbing the inhibitory circuits of MOB and AOB & AOB-alone resulted in the loss of pheromone location memory. 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.