Roles of Adenosine A2A Receptor in Sleep-wake Regulation
作者单位:Department of Pharmacology School of Basic Medical Sciences Fudan University
会议名称:《中国神经科学学会第十二届全国学术会议》
会议日期:2017年
学科分类:0710[理学-生物学] 07[理学] 071006[理学-神经生物学]
关 键 词:adenosine A2A receptor sleep striatum optogenetics chemogenetics
摘 要:Adenosine acts as a homeostatic regulator of sleep. Activation of adenosine A receptor(AR) by its agonist infused into the brain potently increases sleep. The arousal effect of caffeine, an AR and AR antagonist, is dependent on the AR. AR is highly expressed in the striatum. However, the role of AR in the striatum in sleepwake regulation has been paid little attention. We found that optogenetic activation of AR expressing neurons in the nucleus accumbens(NAc) increased non-rapid eye movement(NREM) sleep. Projections of AR neurons from the NAc distributed to nuclei in the forebrain, diencephalon, and brainstem using AAV-hr GFP as a tracer. Moreover, chemogenetic activation of AR neurons in the rostral and central dorsal striatum, but not caudal, induced remarkable increase in NREM sleep. We revealed that dorsal striatal AR neurons innervated the external globus pallidus(GPe) in topographic organizations, and preferentially formed inhibitory synapses with parvarlbumin(PV)-positive neurons in the GPe. Lesions of PV-positive neurons in the GPe abolished an increase in NREM sleep caused by activation of AR neurons in the striatum. In contrast, chemogenetic inhibition of striatal AR neurons increased wakefulness in the active period. Taking together, these findings reveal a prominent contribution of the striatal AR neurons to the control of sleep, and provide these neurons as a therapeutic target to treat sleep disturbances, such as excessive daytime sleepiness in Parkinson’s patients.