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Published June 21, 2017 | Supplemental Material
Journal Article Open

Dorsal Raphe Dopamine Neurons Modulate Arousal and Promote Wakefulness by Salient Stimuli


Ventral midbrain dopamine (DA) is unambiguously involved in motivation and behavioral arousal, yet the contributions of other DA populations to these processes are poorly understood. Here, we demonstrate that the dorsal raphe nucleus DA neurons are critical modulators of behavioral arousal and sleep-wake patterning. Using simultaneous fiber photometry and polysomnography, we observed time-delineated dorsal raphe nucleus dopaminergic (DRNDA) activity upon exposure to arousal-evoking salient cues, irrespective of their hedonic valence. We also observed broader fluctuations of DRNDA activity across sleep-wake cycles with highest activity during wakefulness. Both endogenous DRNDA activity and optogenetically driven DRNDA activity were associated with waking from sleep, with DA signal strength predictive of wake duration. Conversely, chemogenetic inhibition opposed wakefulness and promoted NREM sleep, even in the face of salient stimuli. Therefore, the DRNDA population is a critical contributor to wake-promoting pathways and is capable of modulating sleep-wake states according to the outside environment, wherein the perception of salient stimuli prompts vigilance and arousal.

Additional Information

© 2017 Elsevier Inc. Received 6 October 2016, Revised 31 March 2017, Accepted 11 May 2017, Available online 8 June 2017. Published: June 8, 2017. We would like to acknowledge Drs. Karl Deisseroth and Tom Davidson for the fiber photometry setup. We appreciate the entire Gradinaru lab and Dr. David Anderson for helpful discussions. This work was supported by the NIH (Director's New Innovator grants IDP20D017782-01 and PECASE), the NIH/NIA (grants 1R01AG047664-01 and NIH BRAIN1U01NS090577), the Heritage Medical Research Institute (HMRI-15-09-01), the Pew Charitable Trust (00026171), the Michael J. Fox Foundation (RRIA 2013), Caltech-GIST (CG2013), and the Sloan Foundation (FR2015-65471, to V.G.). J.B.T. is a Colvin postdoctoral fellow. J.E.R. is supported by the Children's Tumor Foundation (2016-01-006). C.X. was partly supported by the Michael J. Fox Foundation.

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August 21, 2023
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