In the adult hippocampus, neuroprogenitor cells in the subgranular zone (SGZ) of the dentate gyrus give rise to newborn neuroblasts. However, only a small subset of these cells integrates into the hippocampal circuitry as mature neurons at the end of a 4 week period. Here, we show that the majority of the newborn cells undergo death by apoptosis in the first 1 to 4 days of their life, during the transition from amplifying neuroprogenitors to neuroblasts. These apoptotic newborn cells are rapidly cleared out through phagocytosis by unchallenged microglia present in the adult SGZ niche. Phagocytosis by the microglia is efficient and undeterred by increased age or inflammatory challenge. Our results suggest that the main critical period of newborn cell survival occurs within a few days of birth and reveal a new role for microglia in maintaining the homeostasis of the baseline neurogenic cascade.
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"n, number of spines. early critical period (1–4 days after cell birth) and a secondary, late critical period (1–3 weeks after cell birth) (Sierra et al., 2010). At the early stage the majority of adult-born cells undergo apoptosis as they develop from late proliferating amplifying neuroprogenitors to early neuroblasts. "
"Microglia, the innate immune cells of the brain, exhibit a dual role in adult neurogenesis. Under physiological conditions, microglia phagocytose apoptotic neuronal progenitor cells and promote neuronal differentiation via trophic factors  . Conversely, following seizures, both detrimental and a supportive role for activated microglia have been described  . "
[Show abstract][Hide abstract] ABSTRACT: Adult hippocampal neurogenesis is modulated by physiological and pathological stimuli, including seizures and inflammation. Here, we describe stable interactions between microglia and newborn neurons using two-photon and confocal microscopy. On 3 weeks-old neurons, these interactions exhibit preferences for distal dendrites under physiological conditions. Conversely, after status epilepticus, ramified microglia, in particular, interact more with the proximal dendrites of new neurons. No such differences were found on 6 weeks-old neurons. Our study demonstrates regional and temporal specificity of the interactions between newborn neurons and microglia during a critical period for homeostasis and synaptic integration.
"While regulation of stem cell behavior due to systemic factors has been little studied until now, recent work from our lab indicates that they may in fact be of paramount importance, particularly after injury (Lin et al., 2015) (see discussion of cues below). Also present in both forebrain niches are microglial cells which have become a focus of great interest in recent years (Ekdahl et al., 2009; Molina-Holgado and Molina-Holgado, 2010; Russo et al., 2011; Sierra et al., 2010; Whitney et al., 2009). Although the exact nature of their interaction with stem cells in the niche remains enigmatic, it is now believed that microglia are important in regulating neurogenesis in the healthy and in the injured/diseased brain. "