, 2006). Our observations of a linear relationship between neurons and NSCs in the lower blade and after social isolation in contrast with transit amplifying dynamics in the upper

blade and after EEE are consistent with activity differences under these conditions. We suggest that regional differences in baseline neuronal activity and activity changes in response to a changing environment underlie regulation of the NSC lineage. We therefore propose a form of cellular plasticity where the brain responds to changes in the environment by shifting the dynamics of both stem cell differentiation and survival and thus altering the fate of the adult-born stem cell lineage. In our model, NSCs accumulate under deprived conditions resulting in increased neurogenic potential when more favorable conditions return. Such cellular plasticity AMPK inhibitor would provide additional computational units, potentially needed BYL719 datasheet when enriched environments tax hippocampal function. The CreERT2 sequence was removed from pCreERT2 (AA2)

(Feil et al., 1997) (a generous gift from P. Chambon) by EcoRI and inserted into the XhoI of pNerv-SXN (Josephson et al., 1998) (a generous gift from R. Josephson). Orientation of the gene was confirmed by sequencing. Nestin-CreERT2 transgenic mice were created by pronuclear injection of a SalI digest of pNerv-SXN-CreERT2 into fertilized embryos. Nestin-CreERT2 animals were bred with R26R enhanced yellow fluorescent protein (EYFP) reporter mice (Srinivas et al., 2001). All genotypes were confirmed by PCR. through Animals aged 8–12 weeks were administered 5 mg of tamoxifen (Sigma, St. Louis, MO) suspended in 100 μl 1:1 honey:water mixture by gavage once a day for 4–5 days or twice, 12 hr apart (experiments 1F–K, 2, 3F, S2A, S3). Animals were administered TMX in their home cages and then placed in their experimental

environments. X-irradiated animals were administered TMX while undergoing enrichment. Animals were administered BrdU (150 mg/kg IP) once with the first TMX administration (1F-K), twice with the final two TMX administrations (S3), and on four consecutive days (S6A,B). Standard-housed animals were kept in standard laboratory cages, 4–5 animals per cage, and sacrificed 24 hr (n = 3), 48 hr (n = 5), 5 days (n = 3), 2 weeks (n = 2), 1 month (n = 3, 4), 3 months (n = 3), 6 months (n = 3), or 12 months (n = 6) after the first day of TMX. EEE conditions have been previously described (Meshi et al., 2006); however, animals were housed six to an enriched cage. EEE animals were sacrificed 1 (n = 3) or 3 (n = 3) months after TMX. Socially isolated animals were individually housed and sacrificed 1 (n = 4) or 3 (n = 4) months after TMX. Animals in all housing conditions were provided with food and water ad libitum.