Figure 1. GSK3 inhibition suppresses excitability.

(a) Spontaneous AP frequencies (mean±s.e.m.) from 2-min loose-patch recordings of neurons treated with vehicle (0.002% DMSO; black) or CHIR-99021 (CHIR, 1 μM; blue) during the day (ZT 4–8) or early-night (ZT 14–18). CHIR significantly suppressed SCN activity during the day (***P<0.001) but not the night (NS; P=0.608). Two-way ANOVA; treatment X time interaction, F_(1,146)=5.772, P=0.018. From left to right, n=38 cells, 4 animals; 41 cells, 4 animals; 38 cells, 3 animals; 33 cells and 3 animals. (b) Representative cell-attached loose-patch traces (10 s) from each group. Scale bar, 1 s. (c) Dot plot of RMP for individual SCN neurons treated with vehicle or CHIR during the mid-day (ZT 4–8). Symbol colour indicates subgroup phenotype as indicated in the legend. Lines indicate means for Vehicle and CHIR groups. There was no difference in RMP between groups. Independent samples t-test; t₍₆₇₎=−1.521, P=0.133; n=34–35 cells, 5–6 animals per group. (d,e) Representative current clamp traces (5 s) of SCN neurons from each group in c. Scale bar, 10 mV, 1 s. Inset shows depolarizing ramp between APs in control cells. Scale bar, 10 mV, 50 ms.