Fig. 6:

Key findings with the BACHD model were confirmed in the Q175 mouse model. (A) The daily peak of SFR in SCN neurons is reduced in Het and Hom Q175 mice. Using the current-clamp recording technique in the whole-cell configuration, we measured the SFR in dSCN neurons during the day (ZT 5-7) and night (ZT 17-19). Bar graphs plot the mean and SEM for each of the groups. Scatter plots show values for the individual dSCN neurons: WT (white circles, day, n = 10; black circles, night, n = 23); Het Q175 (white upward triangles, day, n = 21; black upward triangles, night, n = 17); Hom Q175 (white downward triangles, day, n = 22; black downward triangles, night, n = 23). The data was analyzed using two-way ANOVA with genotype and time as factors. The Q175 dSCN neurons did not exhibit the day/night difference in SFR seen in WT neurons. * = significant difference between genotypes; # = significant difference between day and night. (B) Current injection (5pA) increased the firing rate in the SCN in WT and Het Q175 mice (n=14 per genotype), but the increase seen in WT is significantly larger than that measured in the Het Q175. Symbols show mean ± SEM of the firing rate before, during, and after current injection. Two-way ANOVA was used to identify significant effects of genotype and treatment on firing rate. * = significant difference between genotypes; # = significant difference between control and treated. (C) BK currents measured in Het Q175 dSCN neurons (n = 9) were significantly larger than those in WT (n = 6) during the day (ZT 5-7). Symbols and error bars represent means ± SEM. Two-way ANOVA was used to identify significant effects of genotype and/or voltage step magnitude on evoked currents. There were significant effects of genotype on the BK current at the 60 and 80 mV steps. * = significant difference between genotypes.