Glycogen synthase kinase 3beta (GSK3β), a downstream molecule of Akt or PKA, is involved in many physiological and pathological processes, such as synaptic plasticity (Ochs et al., 2015), tau pathology of Alzheimer's disease (Hernandez et al., 2013) and ethanol-induced neuronal excitotoxicity (French and Heberlein, 2009; Luo, 2009; Zeng et al., 2012; Shah et al., 2015). The role of GSK3β in the ethanol-induced suppression was tested with SB415286, a GSK3β inhibitor. SB415286 (5 μM) had no effect on control γ power (7.8 ± 2.5%, P > 0.05, vs. baseline, n = 9), but completely blocked ethanol-induced suppression of γ (example in Figure 5A). The effect of 50 mM ethanol in the presence of SB415286 (14.3 ± 7.1%, P > 0.05 vs. SB415286 baseline, n = 9) was completely different from that of ethanol alone (Student t-test P < 0.001 vs. 50 mM ethanol alone, Figure 5B). Similarly, the effect of 100 mM ethanol (28.9 ± 14.1%, P > 0.05 vs. SB415286 baseline, n = 9) was different from that in the absence of SB415286 (Student t-test, P < 0.001 vs. 100 mM ethanol alone, Figure 5B). These results suggest that GSK3β activation is essential for the ethanol-induced suppression of γ oscillations.
