Activation of Ventral Pallidum CaMKIIa-Expressing Neurons Promotes Wakefulness

The ventral pallidum (VP) is involved in the regulation of a variety of behaviors such as motor, reward, and behavioral motivation, and the ability to perform these functions properly is dependent on a high degree of wakefulness. It is unknown whether VP CaMKIIa-expression (VP^CaMKIIa) neurons also have a role in sleep-wake regulation and related neuronal circuit mechanisms. In the present experiment, we first used in vivo fiber photometry to find the population activity of VP^CaMKIIa neurons which increased during the transitions from non-rapid-eye movement (NREM) sleep to wakefulness and NREM sleep to rapid-eye-movement (REM) sleep, with decreased during the transitions from wakefulness to NREM sleep. Then chemogenetic activation of VP^CaMKIIa neurons induced an increase in wakefulness that lasted for 2 h. Mice that were exposed to short-term optogenetic stimulation woke up quickly from stable NREM sleep, and long-term optogenetic stimulation maintained wakefulness. In addition, optogenetic activation of the axons of VP^CaMKIIa neurons in the lateral habenula (LHb) also facilitated the initiation and maintenance of wakefulness and mediated anxiety-like behavior. Finally, the method of chemogenetic inhibition was employed to suppress VP^CaMKIIa neurons, and yet, inhibition of VP^CaMKIIa neuronal activity did not result in an increase in NREM sleep and a decrease in wakefulness. Overall, our data illustrate that the activation of VP^CaMKIIa neurons is of great importance for promoting wakefulness.