Differential 24 h responsiveness of Prox1-expressing precursor cells in adult hippocampal neurogenesis to physical activity, environmental enrichment, and kainic acid-induced seizures.

Regulation of adult hippocampal neurogenesis in mice responds to behavioral stimuli, including physical activity (RUN) and the exposure to enriched environments (ENR). If studied after days or weeks, these stimuli and the pathological stimulus of kainic acid-induced seizures (KA) show differential effects on different developmental stages of adult neurogenesis. The question thus arose, whether such differential effects would also be apparent under very acute conditions. To further refine our method for identifying key restriction points in adult neurogenesis we here used the first expression of granule cell-specific transcription factor prospero-related homeobox 1 (Prox1) to identify lineage-determined progenitor cells in a nestin-green fluorescent protein (GFP) reporter gene mouse and labeled proliferating precursor cells with bromodeoxyuridine (BrdU). Twenty-four hours after the stimulus adult neurogenesis showed a very similar response to the three paradigms, in that cell proliferation increased. Detailed analysis, however, revealed the following new results: (1) KA, but not RUN and ENR stimulated the division of radial glia-like type-1 cells, (2) KA led to the disappearance of proliferative undetermined progenitor cells (type-2a), (3) only RUN increased proliferation of type-2a cells, (4) ENR and KA, in contrast, acted on lineage-determined progenitor cells (type-2b and type-3) even under acute conditions, and (5) only in the case of KA the short-term stimulus resulted in measurably increased survival of newborn neurons 4 weeks later. These results confirm and specify the idea that in the course of neuronal development in the adult hippocampus, precursor cells acutely sense and distinguish various forms of "activity" differentially and translate these stimuli into defined responses based on their stage of development.