Sensory experience-dependent integration and activation of new neurons in the accessory olfactory bulb of adult female mice

Interneurons in the main and accessory olfactory bulbs (MOB, AOB) undergo life-long turn-over. In the AOB, inhibitory granule cells in the glomerular (gl-l), external plessiform (epl) and granular layer (gr-l) are continuously replaced by immature precursors migrating from the sub-ventricular zone (SVZ). Sensory input plays a prominent role in newly-generated cell survival and maturation. In the AOB of adult female mice, the survival of these neurons increases after chronic exposures to male soiled bedding containing pheromones, chemical signals that convey social information between members of the same species. Male pheromones become attractive for females mice and this form of associative learning involves regions of the vomeronasal (VNS) system to which the AOB projection neurons send afferents. One month after their genesis, new neurons are functionally integrated into the AOB but it remains unclear when these cells are preferentially recruited into this plastic adult circuitry and whether they support any specific sensory function. To address these issues, we analyzed the sensory driven positive selection of newborn AOB granule cells in adult females after exposure to soiled bedding. We found that AOB newborn cells undergo positive selection by short term exposure to male pheromones one week after their genesis. To determine whether and when newly generated AOB cells become involved in the processing of male individual stimuli, we quantified the percentage of newly-generated neurons activated by experienced or novel male bedding, by evaluating the expression of c-fos, a marker for neuronal activity. We found that AOB newborn cells are specifically recruited shortly after their integration by experienced male individual pheromones; this functional recruitment is transient and is specific for newly born neurons, as older ones do not show a similar response. Taken together these results suggest that newly-generated cells integrated in AOB circuitry are important in the AOB signal transduction and they can lead significant individual odour information to brain centres related to the vomeronasal pathway. In fact, we show that the activity in downstream nuclei of this pathway is modulated as a consequence of this neurogenesis upregulation, after bedding exposure.