title: 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.
authors.affiliation: State key Laboratory of Medical Neurobiology and Department of Neurobiology, School of Basic Medical Science, Fudan University, Shanghai 200032, China Department of Neurology and Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Mei-Hong
authors.initials: MH
authors.lastname: Qiu
authors.affiliation: Department of Neurology and Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Qiao-Ling
authors.initials: QL
authors.lastname: Yao
authors.affiliation: Department of Neurology and Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Ramalingam
authors.initials: R
authors.lastname: Vetrivelan
authors.affiliation: Department of Neurology and Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Chen
authors.affiliation: Department of Neurology and Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D059290:Dopaminergic Neurons / Q000502:physiology*; D005917:Globus Pallidus / Q000502:physiology*; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D065842:Pars Compacta / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep; D014851:Wakefulness
chemical_list: D004298:Dopamine
keywords: Parkinson's disease; dopamine; globus pallidus; sleep; substantia nigra pars compacta