Neurogenesis and Oligodendrogenesis in the Adult Ventricular-Subventricular Zone During Pregnancy

Adult neurogenesis is an important form of brain plasticity, and mainly occurs in two regions of the adult rodent brain, the ventricular-subventricular zone (V-SVZ) and the subgranular zone of the hippocampal formation. Adult neural stem cells (NSCs) in the V-SVZ generate neurons and a small number of glia throughout life. They possess a regional identity, and depending on their location in the niche, give rise to different subtypes of olfactory bulb interneurons. The functional significance of such stem cell and interneuron diversity is not fully understood. Hunger and satiety were recently shown to regulate one distinct stem cell pool in the ventral V-SVZ. As such, physiological states may recruit different pools of stem cells. The result of increased stem cell activity is only seen with a delay of 14 days, as it takes this time for a newly-generated interneuron to mature. We therefore hypothesized that different physiological states could regulate stem cells "on demand" as a way to anticipate interneuron need in the near future.
Here we describe that pregnancy induces the temporally coordinated recruitment of stem cells in different regional domains of the V-SVZ. Tightly controlled generation of new neurons during early pregnancy leads to the addition of distinct interneurons into different layers of the olfactory bulb, which become functional during onset of maternal care. Some subtypes of pregnancy-associated interneurons are short-lived, and their transient addition into the circuit might reflect temporary increased demand for their function. In the granule cell layer of the olfactory bulb, the transient increase in pregnancyassociated neurons in the perinatal care period is accompanied by a temporary rise in oligodendrocyte precursor cells. In short, dynamic stem cell recruitment during early pregnancy for the generation of diverse interneurons with different survival rates prepares the brain for maternal needs during the postpartum period.
Pregnancy has been demonstrated to increase oligodendrogenesis in the corpus callosum. It is unknown whether NSCs in the V-SVZ, which also generate oligodendrocytes, contribute to this increase. Here, we identify two cycling populations of oligodendroglial cells in the V-SVZ with unknown lineage relationship, branchy PDGFRα+ oligodendrocyte precursor cells and PDGFRα- transit-amplifying cells. Oligodendrogenesis increases during early pregnancy in both white and grey matter around the V-SVZ. In the corpus callosum, newborn oligodendroglial cells are predominantly found in the area above the V-SVZ, hinting at an origin in the germinal niche. There, however, neither PDGFRα+ oligodendrocyte precursor cells nor PDGFRα- transit amplifying cells seem to be regulated by pregnancy in any of the analyzed domains.
In sum, different physiological states, including pregnancy, regulate neurogenesis but not necessarily oligodendrogenesis in the V-SVZ in a regional manner. Time, space and physiological context are key to understand the functional relevance of stem cell- and interneuron heterogeneity.