Coordinations of locomotor and respiratory rhythms in vitro are critically dependent on hindlimb sensory inputs.

A 1:1 coordination between locomotor and respiratory movements has been described in various mammalian species during fast locomotion, and several mechanisms underlying such interactions have been proposed. Here we use an isolated brainstem-spinal cord preparation of the neonatal rat to determine the origin of this coupling, which could derive either from a direct interaction between the central locomotor- and respiratory-generating networks themselves or from an indirect influence via a peripheral mechanism. We demonstrate that during fictive locomotion induced by pharmacological activation of the lumbar locomotor generators, a concomitant increase in spontaneous respiratory rate occurs without any evident form of phase coupling. In contrast, respiratory motor activity can be fully entrained (1:1 coupling) over a range of periodic electrical stimulation applied to low-threshold sensory pathways originating from hindlimb muscles. Our results provide strong support for the existence of pathways between lumbar proprioceptive afferents, medullary respiratory networks, and phrenic motoneurons that could provide the basis of the locomotor-respiratory coupling in many animals. Thus a peripheral sensory system involved in a well defined rhythmic motor function can be responsible for the tight functional interaction between two otherwise independent motor behaviors.

Ontogeny of descending serotonergic innervation and evidence for intraspinal 5-HT neurons in the mouse spinal cord.

Neuronal networks in the mouse spinal cord express serotonin (5-HT)-induced rhythmic motor activity at early developmental stages (embryonic day (E) 12.5). Later in development, by post-natal day (P) 10, the 5-HT-evoked rhythmic motor activity matures and acquires an adult locomotor-like pattern. With the view to establishing a relationship between the ontogeny of locomotor networks and the maturation of spinal 5-HT systems, we have traced 5-HT immunoreactivity in the mouse spinal cord from E12.5 to PN10. By E12.5, descending 5-HT immunoreactive (5-HT-ir) fibers that likely originate from raphe nuclei were detected in the ventral and lateral funiculi, at anterior cervical spinal levels, but not at more caudal levels. Descending 5-HT-ir axons reached thoracic levels at E14.5 and lumbar levels at E16.5. Some 5-HT-ir fibers could be detected in the ventral and intermediate gray matter by E16.5, whereas the dorsal gray matter was not invaded before PN0. At PN10, a dense serotonergic innervation was restricted to the gray matter with a high concentration of 5-HT-ir fibers in three areas: dorsal horn, ventral horn (where motoneurons are located) and intermediate area. Surprisingly, from E16.5 to PN10, 5-HT-ir intraspinal neurons were found, exclusively at sacral levels. Their somata lay in the gray matter around the central canal and preferentially in the ventro-median part of the ventral horn. The functional significance of these sacral 5-HT-ir neurons is discussed.