UC San Diego

While nAChRs are poised to regulate adult neurogenesis in the dentate gyrus of the hippocampus, a careful examination of the effects of nicotinic signaling on adult neurogenesis has not been performed. Here we examine, in vivo, the maturation and survival of adultborn neurons from nAChR knockout mice or mice receiving nAChR agonists. We find that endogenous, cell autonomous signaling through [alpha]7-nAChRs is necessary for proper maturation, synaptic integration, and survival of adultborn neurons. Nicotine exposure at levels relevant for human smokers acts through the same receptor to kill young adultborn neurons, and increase survival of the more mature population. Independent of effects on survival, nicotine enhances dendritic growth and spine formation of adultborn neurons. DMXBA, a partial [alpha]7-nAChR agonist, can be used to increase dendritic growth without eliciting detrimental effects on survival. These results demonstrate a profound role for nAChR signaling in controlling the fate of adultborn neurons in the dentate gyrus of the hippocampus