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Abstract
New neurons are generated in the adult hippocampus throughout life by neural stem/progenitor
cells (NSCs), and neurogenesis is a plastic process responsive to external stimuli.
We show that canonical Notch signaling through RBP-J is required for hippocampal neurogenesis.
Notch signaling distinguishes morphologically distinct Sox2(+) NSCs, and within these
pools subpopulations can shuttle between mitotically active or quiescent. Radial and
horizontal NSCs respond selectively to neurogenic stimuli. Physical exercise activates
the quiescent radial population whereas epileptic seizures induce expansion of the
horizontal NSC pool. Surprisingly, reduced neurogenesis correlates with a loss of
active horizontal NSCs in aged mice rather than a total loss of stem cells, and the
transition to a quiescent state is reversible to rejuvenate neurogenesis in the brain.
The discovery of multiple NSC populations with Notch dependence but selective responses
to stimuli and reversible quiescence has important implications for the mechanisms
of adaptive learning and also for regenerative therapy.