Ventral pallidal glutamatergic neurons regulate wakefulness and emotion through separated projections

Yan-Jia Luo; Jing Ge; Ze-Ka Chen; Zi-Long Liu; Michael Lazarus; Wei-Min Qu; Zhi-Li Huang; Ya-Dong Li

doi:10.1016/j.isci.2023.107385

Ventral pallidal glutamatergic neurons regulate wakefulness and emotion through separated projections

iScience. 2023 Aug 5;26(8):107385. doi: 10.1016/j.isci.2023.107385. eCollection 2023 Aug 18.

Authors

Yan-Jia Luo^{1

2}, Jing Ge¹, Ze-Ka Chen¹, Zi-Long Liu¹, Michael Lazarus³, Wei-Min Qu¹, Zhi-Li Huang^{1

4}, Ya-Dong Li^{1

5}

Affiliations

¹ Department of Pharmacology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
² Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
³ International Institute for Integrative Sleep Medicine (WPI-IIIS) and Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
⁴ Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
⁵ Songjiang Research Institute, Shanghai Songjiang District Central Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201699, China.

Abstract

Insomnia is often comorbid with depression, but the underlying neuronal circuit mechanism remains elusive. Recently, we reported that GABAergic ventral pallidum (VP) neurons control wakefulness associated with motivation. However, whether and how other subtypes of VP neurons regulate arousal and emotion are largely unknown. Here, we report glutamatergic VP (VP^Vglut2) neurons control wakefulness and depressive-like behaviors. Physiologically, the calcium activity of VP^Vglut2 neurons was increased during both NREM sleep-to-wake transitions and depressive/anxiety-like behaviors in mice. Functionally, activation of VP^Vglut2 neurons was sufficient to increase wakefulness and induce anxiety/depressive-like behaviors, whereas inhibition attenuated both. Dissection of the circuit revealed that separated projections of VP^Vglut2 neurons to the lateral hypothalamus and lateral habenula promote arousal and depressive-like behaviors, respectively. Our results demonstrate a subtype of VP neurons is responsible for wakefulness and emotion through separated projections, and may provide new lines for the intervention of insomnia and depression in patients.

Keywords: Behavioral neuroscience; Biological sciences; Natural sciences; Neuroscience; Systems neuroscience.