Editorial on the Research Topic Neuromodulatory Control of Spinal Function in Health and Disease The classical ionotropic transmitters glutamate/ACh (acetylcholine) and glycine/GABA (gamma-amino butyric acid) are, respectively, responsible for the primary excitatory and inhibitory synaptic actions within spinal cord anatomical circuits, be they simple reflexes as the monosynaptic stretch reflex (and its reciprocal inhibition of antagonists), or more distributed and integrated networks along autonomic, sensory, and motor systems. The selection and complex spatiotemporal recruitment of intrinsic spinal circuits (e.g., locomotion) are profoundly sculpted by neuromodulation acting both at pre- and post-synaptic levels. Neuromodulation denotes to the ability of neurons to alter their electrical and synaptic properties in response to intracellular biochemical changes. Neuromodulation commonly occurs via activation of metabotropic (G protein-coupled) receptors that alter signal transduction pathways. Neuromodulators function to modulate rather than mediate activity and represent a broad class of neuroactive substances. By altering the cellular/synaptic properties of individual neurons embedded in networks, neuromodulators profoundly alter the operation of neural circuits and behavior. They provide flexibility in circuit selection and strength to allow the nervous system to adapt neural output according to the functional requirements and/or demands of the individual to achieve the desired behavioral state. At times, it appears that the neuromodulators have a more primary function in activating and controlling complex networks than the term “modulator” would tend to imply. Neuromodulatory transmitter systems undoubtedly affect all spinal cord functional systems including locomotion, respiration (via phrenic and other respiratory motoneurons), posture, balance, fine movements, autonomic functions (including control of bowel, bladder, blood pressure, and heart rate), reflexes, and sensory information processing (nociception, etc.). Since many neuromodulatory transmitter systems (e.g., such as those releasing monoamines) originate from neurons outside of the spinal cord, injuries to the spinal cord will necessarily damage their descending projections in addition to other non-neuromodulatory pathways controlling the anatomical network. Such injuries will therefore affect not only the initiation and control of spinal networks, but also the ability to adjust their output according to ongoing functional demands. The present Research Topic includes review and original research articles that seek to shed light on the neural processes underlying the neuromodulatory control of spinal cord function in health and disease. This Research Topic consists of 24 articles on various aspects of Spinal Cord research contributed by 105 authors. The assembled contributions are summarized below in three thematic categories: (i) locomotion, (ii) descending and segmental pathways, and (iii) disease/injury. The mesencephalic locomotor region (MLR) activates spinal locomotor generating neurons via pathways originating in the medial reticular formation and descending through the ventral funiculus. There is evidence that monoaminergic pathways are also activated both during MLR-evoked fictive locomotion and during spontaneous or voluntary locomotion. In the present original research, Noga et al. measured in real time, by fast-cyclic in vivo voltammetry, the release of the monoamines serotonin (5-HT) and norepinephrine (NE) in the decerebrate cat's lumbar spinal cord during MLR-evoked fictive locomotion. The time course, the spinal locations and the concentration of the release of these two monoamines were mapped. Monoamine release was observed in dorsal horn, intermediate zone/ventral horn. The results demonstrate that spinal monoamine release is modulated on a timescale of seconds, and that the concentrations are high enough to strongly activate various receptors subtypes and further suggest that monoamine action is, in part, mediated by extrasynaptic neurotransmission in the spinal cord. The review by Sharples et al. focuses on the role of dopamine in the spinal control of locomotion in vertebrates. It summarizes the biochemistry, pharmacology, anatomy, and function of dopamine (and to a lesser extent other monoamines) in the locomotor networks of various vertebrates including fish (lamprey and zebrafish), amphibians (larval xenopus), and mammalians (rodents). A brief discussion of the effects of dopamine on rhythmicity in invertebrates is also provided. Parallels are drawn with both noradrenergic and serotonergic systems. New experimental approaches (optogenetics, pharmacogenetics) together with more traditional approaches (intrathecal administration/cell transplantation) to the study of dopaminergic function and/or the treatment of gait disorders following SCI are discussed. Sensorimotor transformations are essential for control of goal-directed behavior and interaction with the outside world. The review by Daghfous et al. examines how the vertebrate CNS integrates sensory signals to generate locomotor behavior by examining the pathways and mechanisms involved in the transformation of cutaneous and olfactory inputs into motor output in the lamprey. The review also explores how serotonin modulates the system through actions on both sensory inputs and motor output. This timely review of mechanisms for sensory control of locomotion is also very thorough and helpful to the uninitiated in this area of lamprey pharmacology. Wienecke et al. studied the interaction between blood pressure, respiration, and locomotor activities in decerebrate cats. They observed periodic variation (Mayer waves) in blood pressure, which was synchronized with respiratory and locomotor drive potentials recorded in hindlimb motoneurons. The report demonstrates the intricate interrelations between...