dopaminergic neurons, with about 20% glutamatergic neurons. Neurons containing the Asn-398 allele exhibited an increase in the amplitude and frequency of spontaneous excitatory post synaptic currents, compared to Asp-398 neurons (Oni et al., 2016). Glutamatergic neurons, but not DA neurons, displayed similar baseline electrophysiological characteristics across genotypes, but had an increased excitatory response to nicotine stimulation and faster receptor desensitization in the Asn-398 variant (Oni et al., 2016). Analysis of the dopaminergic neuron transcriptome by RNAseq revealed significant functional enrichment for pathways specific for calcium signaling, axon guidance, and ligand-receptor interaction (Oni et al., 2016). Due to the young age of these hiPSC-derived neurons, these results suggest the CHRNA5 risk variant may underlie predisposition to nicotine dependence (Oni et al., 2016).
