Adult stem cells are the pillar of tissue homeostasis and repair lifelong. In the adult mammalian brain, only two specific zones retain the ability to proliferate and sustain stemness. The largest neurogenic niche is the Ventricular Sub-Ventricular Zone (V-SVZ), located along the lateral ventricles. Adult neural stem cells (NSCs) in the V-SVZ are molecularly and spatially heterogeneous. Distinct sub-populations give rise to different subtypes of olfactory bulb (OB) interneurons depending on their position within the niche and their developmental identity. Recently, we have shown that pregnancy in mice triggers the recruitment of regionally-distinct adult NSC pools, generating new neurons which integrate into OB anatomical layers that are very lowly remodeled under homeostasis. Interestingly, these pregnancy-related neurons are transient but behaviorally-relevant for the mother. They are functional during the first week of perinatal care and play an important role in own versus alien pup odor recognition. They then disappear from the OB around weaning. However, the cellular and molecular mechanisms underlying the clearance of pregnancy-generated neurons remain unknown.

We performed Visium spatial transcriptomics and machine learning-based cell-type deconvolution to compare OBs from mothers at different stages with virgins. This revealed increased senescence scores in anatomical layers which are specifically remodeled during motherhood, and a striking cell-type propensity to enter senescence. Our in silico data indicate that senescence could play a novel role in circuit plasticity in the maternal brain, by possibly preparing it for the integration and/or clearance of pregnancy-related neurons.

Our preliminary in vivo analyses confirmed a dynamic change of senescence during motherhood, with a peak around the first week of perinatal care, and a significant drop at peri-weaning. We showed that both neuronal and non-neuronal cells can enter senescence, with distinct secretory profiles. Altogether, our work suggests that senescence in the OB of mothers may sustain the integration and then the disappearance of newly-generated neurons during pregnancy. The molecular mechanisms triggering senescence during motherhood, as well as the exact functional impact of this process on newborn neuron survival, and therefore maternal behavior, are still to be elucidated.