Local origin and activity-dependent generation of nestin-expressing protoplasmic astrocytes in CA1

Since reports that precursor cells in the adult subventricular zone (SVZ) contribute to regenerative neuro- and gliogenesis in CA1, we wondered whether a similar route of migration might also exist under physiological conditions. Permanent labeling of SVZ precursor cells with a lentiviral vector for green fluorescent protein did not reveal any migration from the SVZ into CA1 in the intact murine brain. However, in a nestin-GFP reporter mouse we found proliferating cells within the corpus callosum/alveus region expressing nestin and glial fibrillary acidic protein similar to precursor cells in the neighboring neurogenic region of the adult dentate gyrus. Within 3 weeks of BrdU administration, BrdU-positive nestin-GFP-expressing protoplasmic astrocytes emerged in CA1. Similar to precursor cells isolated from the dentate gyrus and the SVZ, nestin-GFP-expressing cells from corpus callosum/alveus were self-renewing and multipotent in vitro, whereas cells isolated from CA1 were not. Nestin-GFP-expressing cells in CA1 differentiated into postmitotic astrocytes characterized by S100β expression. No new neurons were found in CA1. The number of nestin-GFP-expressing astrocytes in CA1 was increased by environmental enrichment. We conclude that astrogenesis in CA1 is influenced by environmental conditions. However, SVZ precursor cells do not contribute to physiological cellular plasticity in CA1.