Dlight dopamine sensor3/10/2023 ![]() These findings suggest that nigrostriatal dopamine is crucial for wakefulness. Moreover, our previous study showed that genetic deletion of D 2Rs significantly decreases wakefulness in mice ( Qu et al., 2010). D 1R and D 2R agonists have been shown to dramatically promote wakefulness ( Ongini et al., 1985 Monti et al., 1989). The dorsal striatum expresses dopamine D 1 and D 2 receptors (D 1Rs, D 2Rs) at high levels ( Weiner et al., 1991 Levey et al., 1993). Lesioning the dorsal striatum decreases and destabilizes wakefulness in rats ( Qiu et al., 2010). Patients with PD have been reported to suffer from severe sleep disorders including insomnia, sleep fragmentation, excessive daytime sleepiness (EDS), and rapid eye movement (REM) sleep behavior disorders ( Adler and Thorpy, 2005). Dysregulation of the striatum and nigrostriatal dopamine are considered to be responsible for Parkinson’s disease (PD). 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.ĭopamine 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). Finally, despite both modafinil and caffeine being wake-promoting agents that increased wakefulness, modafinil increased striatal dopamine levels while caffeine did not. 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. Moreover, the striatal dLight1.1 signal increased significantly during NREM sleep-to-wake transitions, while it decreased during wake-to-NREM sleep transitions. 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. 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. However, whether striatal dopamine levels correlate with vigilance states still remains to be elucidated. Destruction of nigrostriatal dopaminergic neurons or dorsal striatum disrupts the sleep–wake cycle.
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