Activation of adenosine A2A receptors in the olfactory tubercle promotes sleep in rodents.

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 A 2A receptors (A 2A Rs), which are important in sleep regulation. Therefore, we hypothesized that the OT regulates sleep via A 2A 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 A 2A Rs pharmacologically and OT A 2A R neurons via chemogenetics increased non-rapid eye movement sleep for 5 and 3 h, respectively, while blockade of A 2A Rs decreased non-rapid eye movement sleep. Tracing and electrophysiological studies showed OT A 2A R neurons projected to the ventral pallidum and lateral hypothalamus, forming inhibitory innervations. Together, these findings indicate that A 2A Rs in the OT play an important role in sleep regulation. • Activation of OT A 2A Rs increased NREM sleep. • Blockade of OT A 2A Rs increased sleep latency. • Chemogenetic activation of OT A 2A R neurons increased NREM sleep. • Connections between OT A 2A R neurons and neurons in the VP and LH were inhibitory. • The study concluded that the OT promotes sleep through A 2A Rs and A2AR neurons. [ABSTRACT FROM AUTHOR]