Nigrostriatal Dopamine Acting on Globus Pallidus Regulates Sleep

Abstract

Lesions of the globus pallidus externa (GPe) produce a profound sleep loss (∼45%) in rats, suggesting that GPe neurons promote sleep. As GPe neuronal activity is enhanced by dopamine (DA) from the substantia nigra pars compacta (SNc), we hypothesized that SNc DA via the GPe promotes sleep. To test this hypothesis, we selectively destroyed the DA afferents to the caudoputamen (CPu) using 6-hydroxydopamine and examined changes in sleep-wake profiles in rats. Rats with 80-90% loss of SNc neurons displayed a significant 33.7% increase in wakefulness (or sleep reduction). This increase significantly correlated with the extent of SNc DA neuron loss. Furthermore, these animals exhibited sleep-wake fragmentation and reduced diurnal variability of sleep. We then optogenetic-stimulated SNc DA terminals in the CPu and found that 20-Hz stimulation from 9 to 10 PM increased total sleep by 69% with high electroencephalograph (EEG) delta power. We finally directly optogenetic-stimulated GPe neurons and found that 20-Hz stimulation of the GPe from 9 to 10 PM increased total sleep by 66% and significantly increased EEG delta power. These findings elucidate a novel circuit for DA control of sleep and the mechanisms of abnormal sleep in BG disorders such as Parkinson's disease and Huntington's disease.

Developmental ethanol exposure-induced sleep fragmentation predicts adult cognitive impairment

“…This induced change in excitation/inhibition balance could modify both plasticity and function of forebrain circuits underlying cognition and emotion (Hensch, 2005, Sadrian et al, 2013). However, GABAergic neurons are also important for sleep-related oscillations and switching between sleep states (Hermanstyne et al, 2010, Halassa et al, 2011, Abel et al, 2013, Qiu et al, 2014, Brown and McKenna, 2015, Xu et al, 2015), and impaired function of GABAergic neurons impairs sleep (Kalume et al, 2015). If developmental EtOH exposure impairs GABAergic neuron function and/or reduces GABAergic cell number in subcortical areas known to regulate sleep, this may be an important link between early ethanol and sleep, as well as a potential therapeutic target.…”

Deep brain stimulation in the globus pallidus externa promotes sleep

“…Inputs that influence GPe neuronal activity regulate sleep. For example, dopamine from the SNc acting on D 2 receptors in the striatum enhances GPe activity and promotes sleep (Qiu et al, 2014). We propose that pallidocortical projections regulate sleep (Chen et al, 2015).…”

“…MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) lesions of the SNc in primates reduce total sleep amounts and flatten circadian rhythm (Belaid et al, 2014). SNc dopamine signaling in the basal ganglia promotes sleep in rodents (Qiu et al, 2010, Qiu et al, 2014). We postulate that dopamine from the SNc acts on D 2 receptors on striatum inputs to the globus pallidus externa (GPe), disinhibiting the GPe and promoting sleep.…”

Beneficial Effects of Ramelteon on Rapid Eye Movement Sleep Behavior Disorder Associated with Parkinson's Disease - Results of a Multicenter Open Trial

“…Moreover, it has been reported that melatonin protects exogenous L-dopa from autoxidation in the striatum of rats (29). Because the striatal dopamine circuit also regulates sleep quality (30), increased striatal L-dopa bioavailability by melatonin may modulate sleep in patients with PD. In terms of clinical studies, four reports of studies using polysomnography (PSG) have described that melatonin decreases RWA (6)(7)(8)(9).…”