Activation of adenosine A2A receptors in the olfactory tubercle promotes sleep in rodents. (15th May 2020)

• Record Type: Journal Article
• Authors: Li, Rui; Wang, Yi-Qun; Liu, Wen-Ying; Zhang, Meng-Qi; Li, Lei; Cherasse, Yoan; Schiffmann, Serge N.; de Kerchove d'Exaerde, Alban; Lazarus, Michael; Qu, Wei-Min; Huang, Zhi-Li
• Is Part Of: Neuropharmacology. Volume 168(2020)
• Publication Date: 2020-05-15
• Subjects: Olfactory tubercle -- Adenosine A2A receptors -- Non-rapid eye movement sleep -- Chemogenetics; A2AR adenosine A2A receptor -- aCSF artificial cerebral spinal fluid -- AP anteroposterior -- CNO clozapine-N-oxide -- DREADDs designer receptors exclusively activated by designer drugs -- DV dorsoventral -- hrGFP humanized Renilla green fluorescent protein -- LH lateral hypothalamus -- ML mediolateral -- NAc nucleus accumbens -- NREM non-rapid eye movement -- OB olfactory bulb -- OT olfactory tubercle -- REM rapid eye movement -- RT-PCR reverse transcription-polymerase chain reaction -- vGAT vesicular GABA transporter -- vGluT2 vesicular glutamate transporter 2 -- VP ventral pallidum; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2019.107923
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: The olfactory tubercle (OT), an important nucleus in processing sensory information, has been reported to change cortical activity under odor. However, little is known about the physiological role and mechanism of the OT in sleep-wake regulation. The OT expresses abundant adenosine A2A receptors (A2A Rs), which are important in sleep regulation. Therefore, we hypothesized that the OT regulates sleep via A2A Rs. This study examined sleep-wake profiles through electroencephalography and electromyography recordings with pharmacological and chemogenetic manipulations in freely moving rodents. Compared with their controls, activation of OT A2A Rs pharmacologically and OT A2A R neurons via chemogenetics increased non-rapid eye movement sleep for 5 and 3 h, respectively, while blockade of A2A Rs decreased non-rapid eye movement sleep. Tracing and electrophysiological studies showed OT A2A R neurons projected to the ventral pallidum and lateral hypothalamus, forming inhibitory innervations. Together, these findings indicate that A2A Rs in the OT play an important role in sleep regulation. Highlights: Activation of OT A2A Rs increased NREM sleep. Blockade of OT A2A Rs increased sleep latency. Chemogenetic activation of OT A2A R neurons increased NREM sleep. Connections between OT A2A R neurons and neurons in the VP and LH were inhibitory. The study concluded that the OT promotes sleep through A2A Rs and A2AR neurons.