excitatory PSCs (sEPSCs) in both D398 and N398 human excitatory neurons. The frequencies of sEPSCs in both N398 and D398 neurons are stable before the application of nicotine (Fig. 4B–D). However, within 30 s of 0.1 μM nicotine exposure, frequencies of sEPSCs were significantly increased in the N398 subjects compared to the D398 controls (Fig. 4C). Interestingly, following the dramatic increase of the sEPSCs in N398 neurons, the facilitatory effects appeared to decrease over time in the continued presence of nicotine, likely due to the desensitization of the receptor, which mimics the desensitization reported with ectopic expression studies in Xenopus oocytes14. Similarly, the amplitude of response trended higher during the initial 30 s but then fell below D398 shortly thereafter (Fig. 4D). The difference in response at 0.1 μM nicotine was not limited to a single outlier cell or to cells prepared from a single subject (Fig. 4E,F). The distribution of responses was variable but showed clearly that multiple cells from multiple subjects exhibited increased EPSC frequencies and amplitudes.
