Fig. 2: Dopaminergic Hcrtr2-ablated mice exhibit theta and fast-gamma enriched wakefulness. | Molecular Psychiatry

Fig. 2: Dopaminergic Hcrtr2-ablated mice exhibit theta and fast-gamma enriched wakefulness.

From: Inactivation of hypocretin receptor-2 signaling in dopaminergic neurons induces hyperarousal and enhanced cognition but impaired inhibitory control

Fig. 2

a Schematic representation of DAOxR1-KO, DAOxR2-KO, and DAOxR1&2-KO mice. b EEG power spectral density (PSD) analysis of wakefulness in the 3 mutant and control groups averaged across 2 baseline days. PSD values are expressed as percentage of a baseline total power density reference value calculated for each mouse (see SI Methods). Red lines indicate frequency ranges with significant differences. Note logarithmic Y-scales. Insets magnify EEG spectra across 0.75–15 Hz with linear Y-axis. DAOxR2-KO mice show lower delta power (across 3.25–4.75 Hz), but higher theta power (across 6.75–9.75 Hz) compared to DAOxR2-CT mice (two-way ANOVA; genotypeXfrequency interaction F(280,4502) = 1.858, P < 0.001; Tukey post-hoc test, P < 0.05). Wakefulness of DAOxR1&2-KO mice also display lower delta (2–4 Hz), but diminished power extends through inter-delta/theta and slow-theta frequencies (4–7.25 Hz). Only a narrow fast-theta band (8.5–9.75 Hz) shows increased power (two-way ANOVA; genotypeXfrequency interaction F(286,4879) = 1.175, P = 0.026; Tukey post-hoc test, P < 0.05). c Time-frequency heatmaps on the left depict dynamics of the waking EEG in the 3 KO lines across the 3-day recordings as schematized on top. Color-coding represents EEG power calculated across time for each 0.25-Hz frequency bin and expressed relative to mean baseline (BSL) wakefulness during the light phase last 4 h (ZT8-12). Heatmaps on the right depict differential power between KO and controls (CT values are subtracted from KO values, KO-CT). d Time-course analysis of waking delta (1–4 Hz), inter-delta/theta (4–7 Hz), theta (7–11 Hz), and fast-gamma (52.5–80 Hz) band powers. Depicted are EEG powers during wakefulness across time in (averaged) 2 baseline days, 6-h SD and 18 h of recovery, expressed relative to their mean values in baseline ZT8-12 wakefulness (two-way ANOVA; Delta: DAOxR2-KO: baseline: genotype effect F(1,17) = 39.615, P < 0.001; Inter-delta/theta: DAOxR2-KO: baseline: genotype effect F(1,17) = 20.667, P < 0.001; SD: genotype effect F(1,23) = 17.107, P < 0.001; Theta: DAOxR2-KO: baseline: genotype effect F(1,17) = 33.896, P < 0.001, genotypeXtime interaction F(17,288) = 2.159, P = 0.005; SD: genotype effect F(1,23) = 84.493, P < 0.001, genotypeXtime interaction F(23,384) = 1.896, P = 0.008; DAOxR1&2-KO: SD: genotype effect F(1,23) = 10.676, P < 0.001; Fast-gamma: DAOxR2-KO: baseline: genotype effect F(1,17) = 31.217, P < 0.001, genotypeXtime interaction F(17,288) = 1.693, P = 0.043; SD: genotype effect F(1,23) = 73.561, P < 0.001, genotypeXtime interaction F(23,384) = 2.085, P = 0.003; DAOxR1&2-KO: baseline: genotype effect F(1,17) = 6.551, P = 0.011; SD: genotype effect F(1,23) = 5.922, P = 0.015; Bonferroni post-hoc test, *P < 0.05). n = 9 mice per group, except n = 10 for DAOxR1&2-CT.

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