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. Author manuscript; available in PMC: 2020 Feb 22.
Published in final edited form as: Science. 2019 Jan 24;363(6429):880–884. doi: 10.1126/science.aav2546

Fig. 3.

Fig. 3.

Chemogenetic (hM3Dq) activation of glutamatergic supramammillary neurons drives sustained wakefulness without inducing sleep rebound. (A) Diagram depicting Cre-dependent recombination of AAV-DIO-hM3Dq-mCherry in Vglut2-ires-Cre:APPSwe/PS1δE9 mice. (B) Labeling of mCherry-tagged hM3Dq using an anti-DsRed antibody (counterstain cresyl violet, scale bar 500 μm). (C) Timeline of hM3Dq-mediated manipulation of the SuM. (D) EEG data showing significantly increased wakefulness over 9 hours following CNO injection compared to the non-treated day (n=8: 4F, 4M, two-way repeated measures ANOVA, interaction: p<0.0001, Bonferroni post-hoc). (E) NaCl injection in AAV-hM3Dq mice showed no effect on % wakefulness (n=6: 1F, 5M). (F-H) Analysis of % wakefulness (F), % NREM sleep (G) and % REM sleep (H) between 06:00–09:00 (before CNO), 09:00–18:00 (after injection of CNO), and 18:00–06:00 (following night) showed significantly increased wakefulness and decreased sleep following CNO injection (red) compared to the non-treated day (black) but no differences prior to CNO injection. Analysis of the dark period (18:00–06:00) showed similar levels of % wakefulness and sleep in both groups demonstrating a lack of NREM or REM sleep rebound following sustained wakefulness over a period of 9 hrs (two-way repeated measures ANOVA, interaction: p<0.0001, Bonferroni post-hoc). All data represent mean ± SEM. **p<0.01, ***p<0.001.