Adult neurogenesis, the process of generating mature
neurons from adult neural stem cells, proceeds
concurrently with ongoing neuronal circuit activity
and is modulated by various physiological and pathological stimuli. The niche mechanism underlying the
activity-dependent regulation of the sequential steps
of adult neurogenesis remains largely unknown.
Here, we report that neuronal activity decreases the
expression of secreted frizzled-related protein
3 (sFRP3), a naturally secreted Wnt inhibitor highly
expressed by adult dentate gyrus granule neurons.
Sfrp3 deletion activates quiescent radial neural stem
cells and promotes newborn neuron maturation,
dendritic growth, and dendritic spine formation in
the adult mouse hippocampus. Furthermore, sfrp3
reduction is essential for activity-induced adult neural
progenitor proliferation and the acceleration of new
neuron development. Our study identifies sFRP3 as
an inhibitory niche factor from local mature dentate
granule neurons that regulates multiple phases of
adult hippocampal neurogenesis and suggests an
interesting activity-dependent mechanism governing
adult neurogenesis via the acute release of tonic inhibition.