Abstract
Dopamine is involved in numerous neurological processes, and its deficiency has been implicated in Parkinson’s disease, whose patients suffer from severe sleep disorders. Destruction of nigrostriatal dopaminergic neurons or dorsal striatum disrupts the sleep–wake cycle. However, whether striatal dopamine levels correlate with vigilance states still remains to be elucidated. Here, we employed an intensity-based genetically encoded dopamine indicator, dLight1.1, to track striatal dopamine levels across the spontaneous sleep–wake cycle and the dopaminergic response to external stimuli. We found that the striatal dLight1.1 signal was at its highest during wakefulness, lower during non-rapid eye movement (non-REM or NREM) sleep, and lowest during REM sleep. Moreover, the striatal dLight1.1 signal increased significantly during NREM sleep-to-wake transitions, while it decreased during wake-to-NREM sleep transitions. Furthermore, different external stimuli, such as sudden door-opening of the home cage or cage-change to a new environment, caused striatal dopamine release, whereas an unexpected auditory tone did not. Finally, despite both modafinil and caffeine being wake-promoting agents that increased wakefulness, modafinil increased striatal dopamine levels while caffeine did not. Taken together, our findings demonstrated that striatal dopamine levels correlated with the spontaneous sleep–wake cycle and responded to specific external stimuli as well as the stimulant modafinil.
Highlights
Dopamine is involved in numerous behavioral and psychological processes, including motor behavior, attention, motivation, reward, and feeding (Palmiter, 2007; Berke, 2018), all of which operate on the basis of wakefulness (Lazarus et al, 2012, 2013)
Using a dopamine sensor and simultaneous polysomnographic recordings, we demonstrated that striatal dopamine levels were highest during wakefulness and dopamine fluctuations correlated with spontaneous sleep–wake transitions
These findings provide strong evidence that dopamine in the dorsal striatum is important for wakefulness under baseline conditions, induced by cage change or wake-promoting drug modafinil but not caffeine
Summary
Dopamine is involved in numerous behavioral and psychological processes, including motor behavior, attention, motivation, reward, and feeding (Palmiter, 2007; Berke, 2018), all of which operate on the basis of wakefulness (Lazarus et al, 2012, 2013). Dysregulation of the striatum and nigrostriatal dopamine are considered to be responsible for Parkinson’s disease (PD). Lesioning the dorsal striatum decreases and destabilizes wakefulness in rats (Qiu et al, 2010). The dorsal striatum expresses dopamine D1 and D2 receptors (D1Rs, D2Rs) at high levels (Weiner et al, 1991; Levey et al, 1993). Our previous study showed that genetic deletion of D2Rs significantly decreases wakefulness in mice (Qu et al, 2010). These findings suggest that nigrostriatal dopamine is crucial for wakefulness
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