Medial Parabrachial Nucleus Is Essential in Controlling Wakefulness in Rats

Qi Xu; Dian-Ru Wang; Hui Dong; Li Chen; Jun Lu; Michael Lazarus; Yoan Cherasse; Gui-Hai Chen; Wei-Min Qu; Zhi-Li Huang

doi:10.3389/fnins.2021.645877

Medial Parabrachial Nucleus Is Essential in Controlling Wakefulness in Rats

Front Neurosci. 2021 Mar 25:15:645877. doi: 10.3389/fnins.2021.645877. eCollection 2021.

Authors

Qi Xu^{1

2

3}, Dian-Ru Wang^{2

3}, Hui Dong^{2

3}, Li Chen^{2

3}, Jun Lu⁴, Michael Lazarus⁵, Yoan Cherasse⁵, Gui-Hai Chen⁶, Wei-Min Qu^{2

3}, Zhi-Li Huang^{2

3}

Affiliations

¹ Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
² Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
³ State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China.
⁴ Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
⁵ International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan.
⁶ Department of Sleep Disorders and Neurology, The Affiliated Chaohu Hospital of Anhui Medical University, Hefei, China.

Abstract

Activation of the parabrachial nucleus (PB) in the brainstem induced wakefulness in rats, suggesting which is an important nucleus that controls arousal. However, the sub-regions of PB in regulating sleep-wake cycle is still unclear. Here, we employ chemogenetics and optogenetics strategies and find that activation of the medial part of PB (MPB), but not the lateral part, induces continuous wakefulness for 10 h without sleep rebound in neither sleep amount nor the power spectra. Optogenetic activation of glutamatergic MPB neurons in sleeping rats immediately wake rats mediated by the basal forebrain (BF) and lateral hypothalamus (LH), but not the ventral medial thalamus. Most importantly, chemogenetic inhibition of PB neurons decreases wakefulness for 10 h. Conclusively, these findings indicate that the glutamatergic MPB neurons are essential in controlling wakefulness, and that MPB-BF and MPB-LH pathways are the major neuronal circuits.

Keywords: chemogenetics; glutamatergic neurons; optogenetics; parabrachial nucleus; rat; wakefulness.