Whether these proliferating NSCs represent a distinct subpopulation of cells, or whether the stem cell niche can instruct all NSCs to proliferate, remains to be determined.

Our comprehensive in vivo analysis of the adult-born hippocampal NSC lineage reveals that multiple cellular populations survive for extended periods of time and have the capability to accumulate. Along with the potential RNA Synthesis inhibitor to divide, diversity of stem cell progeny can also be instructed by the niche or reflect stem cell heterogeneity. Our results form the basis for an important question: whether the same or different NSCs or IPs produce NSCs, astrocytes, or neurons (Figure 8). Further characterization of the NestinCreERT2 and other genetically defined NSC pools should reveal whether lineage diversity currently ascribed to adult NSCs reflects truly multipotent cells or a heterogeneous pool of committed progenitors and whether all or only

some NSCs can proliferate. We report that modest neurogenesis under standard laboratory housing can dramatically increase to produce over 70,000 neurons Epigenetic signaling pathway inhibitor within three months under more naturalistic conditions of EEE. Hence, persistent adult-born neurongenesis can make a substantial contribution to the 500,000 neuron dentate gyrus (Abusaad et al., 1999 and Kempermann et al., 1998). Accumulation of EYFP+ cells under standard laboratory housing varied greatly with the age of the animals. Age-related decline in adult hippocampal neurogenesis has been well established (Drapeau and Nora Abrous, 2008). Specifically, neurogenesis

decreases much more rapidly between the 1 and 3 month groups (3–4- and 5–6-month-old animals) than between the 3 and 6 month groups (5–6- and 8–9-month-old animals) as demonstrated by several groups using different markers (Seki and Arai, 1995 and Wu et al., 2008). Thus, any gains in EYFP+ cells between 1 and 3 months after TMX are obscured ADAMTS5 by a logarithmic age-related decline in baseline neurogenesis during this time period. However, gains between 3 and 6 months are readily apparent since neurogenesis becomes more constant in this time period. It is also noteworthy that our study design does not distinguish whether one of the genders accounts for the observed differences. Increased variance in the number of EYFP+ neurons in the 12 month group (Figure 4I) with low variance in the number of EYFP+ NSCs in the same animals revealed that the capacity of NSCs for generation of neurons and/or the viability of adult-born neurons varies greatly in older animals. Similarly, the NSC-neuronal relationship differed between the upper and lower blades of the dentate gyrus and between EEE and socially isolated mice.