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

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. [Display omitted] •SPNs in rVMM co-innervate sympathetic and motor regions in the spinal cord•Excitatory and inhibitory rVMM SPNs control motor and sympathetic function oppositely•Excitatory rVMM SPNs set motor and sympathetic tone for locomotion performance•Inhibitory rVMM SPNs regulate muscle atonia and sympathetic hypoactivity in REM sleep The spinal projecting neurons in the rostral ventromedial medulla co-innervate sympathetic preganglionic neurons and motor-related regions in the spinal cord. The excitatory and inhibitory populations in this same brainstem region have opposite functions in regulating somatic and sympathetic tone in different arousal states.