Coupling of excitation and neurogenesis in neural stem/progenitor cells

摘要

Coupling of excitation to neurogenesis in proliferating post-natal NPCs is demonstrated in vitro and in vivo. Neurogenesis is potently enhanced by excitatory stimuli, and involves Ca_v1.2/1.3 channels and NMDA receptors. These Ca²⁺ influx pathways are located on the proliferating NPCs, allowing them to directly sense and process excitatory stimuli. Excitation increases the fraction of NPC progeny that are neurons, and increases total neuron number. Signaling in this pathway leads to rapid induction of a proneural gene expression pattern involving the bHLH genes HES1, Id2, and NeuroD, and the resulting cells become fully functional neurons defined by neuronal morphology, expression of neuronal structural proteins, expression of neuronal TTX-sensitive voltage gated Na⁺ channels, and synaptic incorporation into active neural circuits.