Slow-wave sleep is controlled by a subset of nucleus accumbens core neurons in mice

Abstract

Sleep control is ascribed to a two-process model, a widely accepted concept that posits homoeostatic drive and a circadian process as the major sleep-regulating factors. Cognitive and emotional factors also influence sleep–wake behaviour; however, the precise circuit mechanisms underlying their effects on sleep control are unknown. Previous studies suggest that adenosine has a role affecting behavioural arousal in the nucleus accumbens (NAc), a brain area critical for reinforcement and reward. Here, we show that chemogenetic or optogenetic activation of excitatory adenosine A2A receptor-expressing indirect pathway neurons in the core region of the NAc strongly induces slow-wave sleep. Chemogenetic inhibition of the NAc indirect pathway neurons prevents the sleep induction, but does not affect the homoeostatic sleep rebound. In addition, motivational stimuli inhibit the activity of ventral pallidum-projecting NAc indirect pathway neurons and suppress sleep. Our findings reveal a prominent contribution of this indirect pathway to sleep control associated with motivation.

Modulating Dopamine Signaling and Behavior with Chemogenetics: Concepts, Progress, and Challenges

“…Activation of VTA DAergic neurons by hM3Dq was shown to increase wakefulness periods while reducing sleep-associated behaviors, such as nest building, in both stages of the light/dark cycle in a D 2 R-dependent manner (Oishi et al, 2017a;Sun et al, 2017). Further investigations revealed that NAc D 1 R-and NAc core adenosine A2a receptorexpressing neurons also regulated these sleep-wake patterns (Oishi et al, 2017b;Luo et al, 2018). Activation of D 1 R expressing neurons in the NAc by hM3Dqstimulation prolonged wakefulness and concurrently reduced food intake, while stimulation of the inhibitory hM4Di suppressed arousal and induced sleep behaviors .…”

Sleep and Motor Control by a Basal Ganglia Circuit

“…However, unlike the effect of SNr neuron activation, which rises rapidly within ~20 s of laser onset (Fig. 1b), sleep induction by optogenetic activation of the nucleus accumbens occurs gradually over ~10 min of continuous laser stimulation (Oishi et al, 2017). A subset of GABAergic neurons in the zona incerta, a structure immediately adjacent to the STN, also promotes sleep (Liu et al, 2017).…”

“…Lesion of the globus pallidus also caused severe insomnia in rats (Qiu et al, 2010), which could be due to the loss of GABAergic neurons in the internal segment, a region with strong functional similarity to the SNr (Gerfen and Surmeier, 2011). Chemogenetic activation of adenosine A2A receptor-expressing neurons in the nucleus accumbens (Oishi et al, 2017) or dorsal striatum (Yuan et al, 2017), which can activate the STN and SNr neurons through the indirect pathway (Gerfen and Surmeier, 2011;Kravitz et al, 2010), has been shown to increase NREM sleep. However, unlike the effect of SNr neuron activation, which rises rapidly within ~20 s of laser onset (Fig.…”

GABA neurons in the ventral tegmental area regulate non-rapid eye movement sleep in mice

“…Chemogenetic activation of VTA Gad67+ neurons induced NREM sleep accompanied by higher delta power (slow wave) compared with control conditions (Figure 2g), suggesting that VTA Gad67+ neurons might play a critical role in the generation of slow wave in NREM sleep. Recently, Oishi et al reported that activation of either the cell bodies of GABAergic neurons in the core of NAc or their axonal terminals in the VP enabled evoked slow wave sleep (Oishi et al, 2017b). In addition, activation of GABAergic neurons in the basal forebrain, which includes the VP, produced wakefulness, whereas their inhibition induced sleep (Anaclet et al, 2015).…”