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

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 (A2ARs), which are important in sleep regulation. Therefore, we hypothesized that the OT regulates sleep via A2ARs. 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 A2ARs pharmacologically and OT A2AR neurons via chemogenetics increased non-rapid eye movement sleep for 5 and 3 h, respectively, while blockade of A2ARs decreased non-rapid eye movement sleep. Tracing and electrophysiological studies showed OT A2AR neurons projected to the ventral pallidum and lateral hypothalamus, forming inhibitory innervations. Together, these findings indicate that A2ARs in the OT play an important role in sleep regulation.