Abstract
Nucleus accumbens (NAc) is involved in behaviors that depend on heightened wakefulness, but its impact on arousal remains unclear. Here, we demonstrate that NAc dopamine D1 receptor (D1R)-expressing neurons are essential for behavioral arousal. Using in vivo fiber photometry in mice, we find arousal-dependent increases in population activity of NAc D1R neurons. Optogenetic activation of NAc D1R neurons induces immediate transitions from non-rapid eye movement sleep to wakefulness, and chemogenetic stimulation prolongs arousal, with decreased food intake. Patch-clamp, tracing, immunohistochemistry, and electron microscopy reveal that NAc D1R neurons project to the midbrain and lateral hypothalamus, and might disinhibit midbrain dopamine neurons and lateral hypothalamus orexin neurons. Photoactivation of terminals in the midbrain and lateral hypothalamus is sufficient to induce wakefulness. Silencing of NAc D1R neurons suppresses arousal, with increased nest-building behaviors. Collectively, our data indicate that NAc D1R neuron circuits are essential for the induction and maintenance of wakefulness.
Highlights
Nucleus accumbens (NAc) is involved in behaviors that depend on heightened wakefulness, but its impact on arousal remains unclear
When GCaMP and EEG/EMG signals were recorded in the home cage of mice, we observed that sleep–wake stages were consistently associated with changes in D1 receptor (D1R) neuron population activity (Fig. 1d, f); i.e., during non-rapid eye movement (NREM) sleep, NAc D1R neurons displayed a lower GCaMP signal than during either wakefulness or rapid eye movement (REM) sleep (Fig. 1d, e)
NAc D1R cells began to increase neuronal activities before NREM-towake and NREM-to-REM transitions and decrease neuronal activities before wake-to-NREM transitions (Fig. 1d, f). These findings clearly indicate a mechanistic framework for the participation of NAc D1R neurons in the regulation of sleep and wakefulness
Summary
Nucleus accumbens (NAc) is involved in behaviors that depend on heightened wakefulness, but its impact on arousal remains unclear. The nucleus accumbens (NAc) is the major component of the ventral striatum and has long been studied as a key structure in mediating a variety of neurobiological behaviors including motivation, reward, feeding, learning, and cognition[1]. These higher brain functions operate based on wakefulness[2,3]. Acute cocaine or morphine administration promotes wakefulness[21], showing predominant c-Fos immunoreactivity in D1R neurons in the NAc13,22 These findings suggest that NAc D1R neurons, but not D2R neurons, play important roles in functional modulation of arousal-based behaviors. Our results provide several lines of evidence regarding NAc D1R neuron circuit diagram for arousal control
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