Spinal projecting neurons in rostral ventromedial medulla co-regulate motor and sympathetic tone

Zicong Zhang; Junfeng Su; Jing Tang; Leeyup Chung; Jessica C Page; Carla C Winter; Yuchu Liu; Evgenii Kegeles; Sara Conti; Yu Zhang; Jason Biundo; Joshua I Chalif; Charles Y Hua; Zhiyun Yang; Xue Yao; Yang Yang; Shuqiang Chen; Jan M Schwab; Kuan Hong Wang; Chinfei Chen; Michael J Prerau; Zhigang He

doi:10.1016/j.cell.2024.04.022

Spinal projecting neurons in rostral ventromedial medulla co-regulate motor and sympathetic tone

Cell. 2024 May 3:S0092-8674(24)00447-1. doi: 10.1016/j.cell.2024.04.022. Online ahead of print.

Authors

Zicong Zhang¹, Junfeng Su¹, Jing Tang¹, Leeyup Chung¹, Jessica C Page¹, Carla C Winter², Yuchu Liu¹, Evgenii Kegeles³, Sara Conti¹, Yu Zhang¹, Jason Biundo¹, Joshua I Chalif⁴, Charles Y Hua¹, Zhiyun Yang¹, Xue Yao¹, Yang Yang¹, Shuqiang Chen⁵, Jan M Schwab⁶, Kuan Hong Wang⁷, Chinfei Chen¹, Michael J Prerau⁸, Zhigang He⁹

Affiliations

¹ F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA; Department of Neurology and Ophthalmology, Harvard Medical School, Boston, MA, USA.
² F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA; Department of Neurology and Ophthalmology, Harvard Medical School, Boston, MA, USA; Harvard/MIT MD-PhD Program, Harvard Medical School, Boston, MA, USA.
³ F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA; Department of Neurology and Ophthalmology, Harvard Medical School, Boston, MA, USA; PhD Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA, USA.
⁴ F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA; Department of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USA.
⁵ Graduate Program for Neuroscience, Boston University, Boston, MA, USA.
⁶ Belford Center for Spinal Cord Injury, The Ohio State University, Columbus, OH, USA; Departments of Neurology and Neuroscience, College of Medicine, The Ohio State University, Columbus, OH, USA.
⁷ Department of Neuroscience, University of Rochester Medical Center, Rochester, NY, USA.
⁸ Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
⁹ F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA; Department of Neurology and Ophthalmology, Harvard Medical School, Boston, MA, USA. Electronic address: zhigang.he@childrens.harvard.edu.

PMID: 38733990
DOI: 10.1016/j.cell.2024.04.022

Abstract

Many behaviors require the coordinated actions of somatic and autonomic functions. However, the underlying mechanisms remain elusive. By opto-stimulating different populations of descending spinal projecting neurons (SPNs) in anesthetized mice, we show that stimulation of excitatory SPNs in the rostral ventromedial medulla (rVMM) resulted in a simultaneous increase in somatomotor and sympathetic activities. Conversely, opto-stimulation of rVMM inhibitory SPNs decreased both activities. Anatomically, these SPNs innervate both sympathetic preganglionic neurons and motor-related regions in the spinal cord. Fiber-photometry recording indicated that the activities of rVMM SPNs correlate with different levels of muscle and sympathetic tone during distinct arousal states. Inhibiting rVMM excitatory SPNs reduced basal muscle and sympathetic tone, impairing locomotion initiation and high-speed performance. In contrast, silencing the inhibitory population abolished muscle atonia and sympathetic hypoactivity during rapid eye movement (REM) sleep. Together, these results identify rVMM SPNs as descending spinal projecting pathways controlling the tone of both the somatomotor and sympathetic systems.

Keywords: blood pressure; medulla; motor control; reticulospinal neurons; spinal projecting neurons; sympathetic regulation; sympathetic tone.