Distinct dynamic patterns of dopamine signaling during sleep-wake states.

(A) Schematic illustration depicting the experimental design in which DA sensor was injected into different downstream targets and EEG/EMG were recorded. (B) An example multi-site fiber photometry recording session. Shown are the EEG spectrogram (normalized by the maximum of each session; Freq., frequency), EMG amplitude (Ampl.), brain states (color-coded), and DA signal traces. (C) Temporal changes of DA levels in different brain areas at each transition. For each subpanel: Left, schematic of the DA sensor injection and recording site; Middle, DA activity aligned to brain-state transitions (time zero indicates the transition point; shading represents ±s.e.m.); Right, summary of DA activity during WAKE, NREM, and REM, with each dot representing one animal. (D) Summary of DA activity (normalized to [0 1]) during 4 brain-state transitions across different brain areas. The data shown here is the average across mice.

Correlation patterns of dopamine release during sleep-wake transitions.

(A) Temporal correlation of DA signaling during NREM to WAKE transition states between different brain areas recorded simultaneously. (B) Correlation coefficient of the DA signals during NREM to WAKE transition states between regions. (C) Temporal correlation of DA signaling during NREM to REM transition states between different brain areas recorded simultaneously. (D) Correlation coefficient of the DA signals during NREM to REM transition states between regions.

Laser-evoked VTA and DRN dopamine signaling exhibit distinct response patterns.

(A) Schematic illustration depicting the experimental design in which ChrimsonR and GRAB-DA2m vectors were injected into the VTA, and the DA sensor was injected into different downstream targets. (B) Heatmap of laser-evoked DA response in NAc in one session. Top, 2 s stimulation protocol; Bottom, 10 s stimulation protocol. (C) Laser-evoked DA sensor response in PFC, NAc, DLS, and CeA with the 2 s (averaged peak amplitude: A = 0.35, 2.04, 1.63, 0.17 respectively) or 10 s (averaged peak amplitude: A = 0.36, 1.66, 1.59, 0.20 respectively) stimulation in the VTA. (D) Schematic illustration depicting the experimental design in which ChrimsonR and GRAB-DA2m vectors were injected into the DRN, and the DA sensor was injected into different downstream targets. (E) Heatmap of laser-evoked DA response in PFC in one session. Top, 2 s stimulation protocol; Bottom, 10 s stimulation protocol. (F) Laser-evoked DA sensor response in PFC, DLS, and CeA with the 2 s (averaged peak amplitude: A = 0.65, 0.45, 0.21, 0.10 respectively) or 10 s (averaged peak amplitude: A = 0.77, 0.70, 0.29, 0.29 respectively) stimulation in the DRN. (G) Schematic illustration depicting the experimental design in which ChrimsonR and GRAB-DA2m vectors were injected into the SNc, and the DA sensor was injected into different downstream targets. (H) Heatmap of laser-evoked DA response in NAc in one session. Top, 2 s stimulation protocol; Bottom, 10 s stimulation protocol. (I) Laser-evoked DA sensor response in PFC, NAc, and DLS with the 2 s (averaged peak amplitude: A = 0.18, 0.57, 0.30, 0.43 respectively) or 10 s (averaged peak amplitude: A = 0.24, 0.86, 0.23, 0.44 respectively) stimulation in the SNc.

Activating VTA or DRN dopamine neurons promotes wakefulness.

(A) Schematic illustration depicting the experimental design in which Gq vectors were injected into the VTA. The example image shows viral expression in the VTA. (B) Effect of VTA DA neurons activation on sleep and wake. Summary of the percentages of time in each brain state following CNO or saline injection in VTA. (C) Schematic illustration depicting the experimental design in which Gq vectors were injected into the DRN. The example image shows viral expression in the DRN. (D) Effect of DRN DA neurons activation on sleep and wake. Summary of the percentages of time in each brain state following CNO or saline injection in DRN. (E) Schematic illustration depicting the experimental design in which Gq vectors were injected into the SNc. The example image shows viral expression in the SNc. (F) Effect of SNc DA neurons activation on sleep and wake. Summary of the percentages of time in each brain state following CNO or saline injection in SNc. (G) Summary of average percentages of time in each brain state. (H) Changes in each brain state induced by chemogenetic activation (difference between CNO and saline injections, averaged across 5 h after injection) in mice with Gq expression in VTA, DRN, or SNc.

Dopamine dynamics across brain-state transitions in distinct brain regions.

(A) Schematic of multi-site fiber photometry and EEG/EMG recording. TDT, Tucker-Davis Technologies. (B) Example of DA dynamics across different brain-state transitions. For each row: Left, Schematic of DA sensor injection; middle, example image of DA sensor expression; right, heatmap of DA signal across different transitions.

Correlation patterns of dopamine release during sleep-wake transitions.

(A) Temporal correlation of DA signaling during REM to WAKE transition states between different brain areas recorded simultaneously. (B) Correlation coefficient of the DA signals during REM to WAKE transition states between regions. (C) Temporal correlation of DA signaling during WAKE to NREM transition states between different brain areas recorded simultaneously. (D) Correlation coefficient of the DA signals during WAKE to NREM transition states between regions.

Control experiment for chemogenetic activation.

(A) Schematic of EEG/EMG recording in mice without Gq vectors expression. (B) Summary of the percentages of time in each brain state following CNO or saline injection in DRN. (C) Summary of averaged percentages of time in each brain state.