Fig. 1: TRESK displays rhythmic expression and function in the SCN and is required for diurnal variation in resting membrane potential and spontaneous firing.
From: TRESK is a key regulator of nocturnal suprachiasmatic nucleus dynamics and light adaptive responses
a Tresk staining in the SCN using beta-galactosidase staining in TRESK−/− mice (top panel) and Tresk mRNA in situ hybridisation (magenta colour) with co-immunohistochemistry with VIP (green) in the WT brain (bottom panel). Both staining methods confirmed abundant Tresk expression in the SCN. Scale bars for beta-galactosidase staining are 100 µm and for RNA scope images 200 µm. b RT-qPCR results of 24-h clock gene (Per1 and Per2) as well as Tresk mRNA expression in WT mouse SCN, with Tresk and Per2 mRNA levels peaking just before the night. Clock genes, Tresk and another K2P channel Task-3 expression over 24 h with filled petals showing the peak and empty—nadir of measured expression. n = 3 SCNs for each time point. c In voltage clamp, SCN neurons were held at −60 mV before depolarisation to −25 mV and then subsequently ramped to −135 mV to isolate potassium leak current, in the presence of TTX. TRESK−/− had reduced nocturnal potassium leak current compared to wild type (WT; day, n = 8; night, n = 18; TRESK−/−; day, n = 14; night, n = 20). Two-way ANOVA on log-transformed data; significant effect of genotype, F(1, 55) = 13.08, p = 0.0006; interaction not significant. d Whole-cell, current clamp recordings of SCN neurons. RMP was depolarised by 9 mV during the subjective night in TRESK−/− mice compared to WT mice. (WT; day, n = 14; night, n = 12; TRESK−/−; day, n = 27; night, n = 11). Two-way ANOVA, significant interaction between genotype and time, F(1, 60) = 4.215, p = 0.044). e Spontaneous neuronal firing recorded using a 256-channel MEA. Diurnal variation of firing rate lost in the TRESK−/− mice. Mean firing rate (MFR) calculated by pooling data from all SCN electrodes (WT; day, n = 7; night, n = 8 animals; TRESK−/−; day, n = 7; night n = 5 animals). Two-way ANOVA on log-transformed data; significant interaction between time and genotype, F(1, 1320) = 6.418, p < 0.01). All grouped data are mean ± SEM. *p < 0.05, ***p < 0.001, ****p < 0.0001. Source data are provided as a Source Data file.
