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.sub.v1.2/1.3 channels and NMDA
receptors. These Ca.sup.2+ 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.sup.+ channels, and synaptic incorporation into active
neural circuits.