Dorsal Striatum Dopamine Levels Fluctuate Across the Sleep–Wake Cycle and Respond to Salient Stimuli in Mice

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.

Disrupted Sleep and Circadian Rhythms in Schizophrenia and Their Interaction With Dopamine Signaling

“…Dopamine neurons in both these regions, the VTA and DRN, exhibit differential firing patterns between sleep/wake states, although there are differences in the activity patterns between the two regions. In the DRN, DA populations are primarily wake-active, and interestingly the net increase in their activity at wake onset positively correlates with the duration of the subsequent wake episode (Cho et al, 2017), as it does in the striatum (Dong et al, 2019). Therefore DA levels at wake onset may determine the length of the following wake period, and subsequently influence sleep/wake cycles.…”

“…There are also changes in extracellular DA levels across the spontaneous sleep/wake cycle. The fluctuations vary between brain regions, but generally levels are higher during wakefulness (Léna et al, 2005;Dong et al, 2019;Menon et al, 2019). In the mouse striatum, DA levels also exhibit dynamic changes within periods of wakefulness and at sleep/wake state transitions (Dong et al, 2019).…”

“…The fluctuations vary between brain regions, but generally levels are higher during wakefulness (Léna et al, 2005;Dong et al, 2019;Menon et al, 2019). In the mouse striatum, DA levels also exhibit dynamic changes within periods of wakefulness and at sleep/wake state transitions (Dong et al, 2019). Given the potent wake-promoting activity of DA, it is currently unclear whether this correlation of DA levels with sleep/wake state is dependent on the sleep/wake cycle or whether elevated DA precedes wakefulness onset.…”

G‐protein‐coupled receptor‐based sensors for imaging neurochemicals with high sensitivity and specificity

“…In freely behaving mice, GPCR‐based sensors have been used to report sensory stimulation‒evoked acetylcholine release and behavior‐related dopamine and norepinephrine release using fiber photometry recording and in vivo two‐photon imaging (Fig. c and d) (Jing et al ; Sun et al ; Patriarchi et al ; Corre et al ; Dong et al ; de Jong et al ; Feng et al ; Mohebi et al ). In principle, the GPCR‐based sensors could also be used together with mini‐scopes to achieve real‐time imaging of neurochemicals in free‐behaving animals.…”

Dopamine-gated memory selection during slow wave sleep

“…Ageing decreases the duration of slow wave sleep, and the number and amplitude of spindles (66), with some reporting nearly a 50% reduction in spindle amplitude with advanced age (67). Models in non-aged animals suggest that D2 receptors promote wakefulness (68) and dopamine levels are generally higher during wake than sleep in animals (69). In young healthy adults, direct administration of a dopamine antagonist during slow wave sleep actually increases the duration of slow waves sleep (70).…”