Newborn granule cells in the AOB are the necessary substrate for partner pheromonal recognition in female mice

Interneurons at the first level of olfactory processing, the main and accessory olfactory bulbs (MOB, AOB) are constantly replaced by adult subventricular zone-derived precursors, and although their fate relies on sensory activity, their role in rodent olfaction is still controversial. In the case of AOB of adult female mice, we found the number of newborn cells increases during short-term direct exposure to male bedding - the largest source of pheromones- indicating a preferential role in the processing of male olfactory signals. By functional inactivation of the peripheral olfactory inputs, we demonstrated that this neuronal addition depends on the detection of pheromonal cues by vomeronasal organ and requires centrifugal feedback activity from the amygdala. Moreover, given that mate pheromonal imprinting in mice requires a cellular substrate responding specifically to male individual odors in the AOB, we asked whether AOB new granule cells could have such capability. To answer this question we quantified the percentage of c-Fos/BrdU coexpression induced by familiar (experienced) or unfamiliar male bedding, at different times after granule cell genesis in the AOB; we found that AOB newborn cells specifically respond to experienced male individual cues, shortly and transiently after their integration. This enhanced response shown by newly generated AOB neurons to male individual odors is linked to the activity induced by the same cues in amygdaloid and hypothalamic nuclei,both of which are involved in estrous induction and thus in the pregnancy block response.We proved that the maturation of newborn granule cells can be tuned by perception of male pheromones only in adult females, and, more markedly, by low molecular weight non-volatile fraction of urine, that is implied in pheromonal recognition during mating. In fact, after mating these compounds are the most effective in blocking pregnancy if granule cells in the AOB are not properly inhibiting their signaling. By pharmacological depletion of newly generated bulbar interneurons, we showed a direct role of renewed AOB granule cells in preventing pregnancy block by familiar mating male odours. On the whole these results indicate that adult neurogenesis is essential for specific brain functions including odour learning and mate recognition.