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Activation of Ventral Pallidum CaMKIIa-Expressing Neurons Promotes Wakefulness

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Abstract

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 (VPCaMKIIa) 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 VPCaMKIIa 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 VPCaMKIIa 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 VPCaMKIIa 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 VPCaMKIIa neurons, and yet, inhibition of VPCaMKIIa neuronal activity did not result in an increase in NREM sleep and a decrease in wakefulness. Overall, our data illustrate that the activation of VPCaMKIIa neurons is of great importance for promoting wakefulness.

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Data Availability

Data supporting the results of this study are available from the corresponding author.

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  1. Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, People’s Republic of China

    Yue Li, Xuefen Zhang, Ying Li, Yidan Li & Haibo Xu

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  1. Yue Li
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Contributions

YL and HX: designed this research. YL: wrote the first draft of manuscript and performed animal studies. YL and YL: performed the behaviour test. XZ: performed the immunohistochemistry experiments. Data collection and analysis were performed by all authors. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Haibo Xu.

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Li, Y., Zhang, X., Li, Y. et al. Activation of Ventral Pallidum CaMKIIa-Expressing Neurons Promotes Wakefulness. Neurochem Res 48, 2502–2513 (2023). https://doi.org/10.1007/s11064-023-03915-x

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