Respiration requires the coordinated rhythmic contractions of diverse muscles to produce ventilatory movements adapted to organismal requirements. During fast locomotion, locomotory and respiratory movements are coordinated to reduce mechanical conflict between these functions. Using semi-isolated and isolated in vitro brain stem-spinal cord preparations from neonatal rats, we have characterized for the first time the respiratory patterns of all spinal intercostal and abdominal motoneurons and explored their functional relationship with limb sensory inputs. Neuroanatomical and electrophysiological procedures were initially used to locate intercostal and abdominal motoneurons in the cord. Intercostal motoneuron somata are distributed rostrocaudally from C(7)-T(13) segments. Abdominal motoneuron somata lie between T(8) and L(2). In accordance with their soma distributions, inspiratory intercostal motoneurons are recruited in a rostrocaudal sequence during each respiratory cycle. Abdominal motoneurons express expiratory-related discharge that alternates with inspiration. Lesioning experiments confirmed the pontine origin of this expiratory activity, which was abolished by a brain stem transection at the rostral boundary of the VII nucleus, a critical area for respiratory rhythmogenesis. Entrainment of fictive respiratory rhythmicity in intercostal and abdominal motoneurons was elicited by periodic low-threshold dorsal root stimulation at lumbar (L(2)) or cervical (C(7)) levels. These effects are mediated by direct ascending fibers to the respiratory centers and a combination of long-projection and polysynaptic descending pathways. Therefore the isolated brain stem-spinal cord in vitro generates a complex pattern of respiratory activity in which alternating inspiratory and expiratory discharge occurs in functionally identified spinal motoneuron pools that are in turn targeted by both forelimb and hindlimb somatic afferents to promote locomotor-respiratory coupling.
The coordination of locomotion and respiration is widespread among mammals, although the underlying neural mechanisms are still only partially understood. It was previously found in neonatal rat that cyclic electrical stimulation of spinal cervical and lumbar dorsal roots (DRs) can fully entrain (1:1 coupling) spontaneous respiratory activity expressed by the isolated brainstem/spinal cord. Here, we used a variety of preparations to determine the type of spinal sensory inputs responsible for this respiratory rhythm entrainment, and to establish the extent to which limb movement-activated feedback influences the medullary respiratory networks via direct or relayed ascending pathways. During in vivo overground locomotion, respiratory rhythm slowed and became coupled 1:1 with locomotion. In hindlimb-attached semi-isolated preparations, passive flexion-extension movements applied to a single hindlimb led to entrainment of fictive respiratory rhythmicity recorded in phrenic motoneurons, indicating that the recruitment of limb proprioceptive afferents could participate in the locomotor-respiratory coupling. Furthermore, in correspondence with the regionalization of spinal locomotor rhythmgenerating circuitry, the stimulation of DRs at different segmental levels in isolated preparations revealed that cervical and lumbosacral proprioceptive inputs are more effective in this entraining influence than thoracic afferent pathways. Finally, blocking spinal synaptic transmission and using a combination of electrophysiology, calcium imaging and specific brainstem lesioning indicated that the ascending entraining signals from the cervical or lumbar limb afferents are transmitted across first-order synapses, probably monosynaptic, in the spinal cord. They are then conveyed to the brainstem respiratory centers via a brainstem pontine relay located in the parabrachial/ Kölliker-Fuse nuclear complex.
Simple motor behaviors such as locomotion and respiration involve rhythmic and coordinated muscle movements that are generated by central pattern generator (CPG) networks in the spinal cord and hindbrain. These CPG networks produce measurable behavioral outputs, and thus represent ideal model systems for studying the operational principles that the nervous system uses to produce specific behaviors. Recent advances in our understanding of the transcriptional code that controls neuronal development have provided an entry point into identifying and targeting distinct neuronal populations that make up locomotor CPG networks in the spinal cord. This has spurred the development of new genetic approaches to dissect and manipulate neuronal networks both in the spinal cord and hindbrain. Here we discuss how the advent of molecular genetics together with anatomical and physiological methods has begun to revolutionize studies of the neuronal networks controlling rhythmic motor behaviors in mice. Keywordslocomotion; respiration; spinal cord; CPG; interneuron; mouse genetics Rhythmic motor outputs such as locomotion, respiration and mastication are, in their simplest forms, highly stereotyped motor behaviors. In fish and tadpoles locomotion primarily consists of repetitive lateral bending movements of the axis, which are produced by waves of contraction and relaxation that propagate rostrocaudally along the body axis. In contrast, terrestrial vertebrates propel themselves by flexing and extending their limbs. This more complex mode of locomotion requires extensive coordination between the forelimbs and hindlimbs on each side of the animal and between individual limb joints. The additional demands of land-based locomotion appear to have driven the evolutionary elaboration of the spinal motor circuitry in terrestrial vertebrates, both in terms of numbers and types of neurons, as well as sensory and supraspinal connectivity. In higher vertebrates, the spinal locomotor system has thus evolved into a highly dynamic network that produces a varied and flexible array of motor outputs in response to sensory feedback pathways and descending influences from rubrospinal, reticulospinal, vestibulospinal and corticospinal pathways. Rhythmic motor circuits in the hindbrain and spinal cordThe core neuronal networks that control rhythmic respiratory and locomotor motor behaviors reside in the hindbrain and spinal cord, respectively. These CPG networks generate simple organized motor rhythms in an autonomous manner. Initial efforts to Correspondence to M.G.: goulding@salk.edu decipher the general organization of these simple motor CPGs in vertebrates relied heavily on electrophysiological and pharmacological approaches. Such efforts were greatly aided by the development of in vitro hindbrain-spinal cord preparations in neonatal rodents (Kudo and Yamada, 1987;Smith and Feldman, 1987). In addition to enabling investigators to localize two rhythmic CPGs in the medulla that drive respiratory movements, the preBötzinger complex and parafac...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.